Mitochondria at the Crossroad of Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Aging".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 22030

Special Issue Editor


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Guest Editor
Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Interests: mitochondria; bioenergetics; neuron; calcium; neurodegeneration; cell death; Huntington's disease; Alzheimer's disease

Special Issue Information

Dear Colleagues,

Mitochondria are the key organelles in the aerobic cell. They have multiple functions, which significantly impact cell life and death. Mitochondria are the main consumers of oxygen and producers of ATP, supporting energy-demanding processes in the cell. Mitochondrial oxidative metabolism unavoidably results in generation of reactive oxygen species (ROS), which may significantly contribute to oxidative stress under pathological conditions. Mitochondria play a very important role in calcium signaling by taking up significant amounts of calcium during excessive calcium influx in the cell or substantial calcium release from endoplasmic reticulum.  The calcium overload of mitochondria may induce mitochondrial permeability transition pore that causes mitochondrial depolarization, leading to inhibition of ATP production in mitochondria, and mitochondrial swelling, resulting in the rupture of the mitochondrial outer membrane and release of cytochrome c and other apoptogenic proteins.  Mitochondrial health is maintained by selective elimination of damaged organelles in the process of mitophagy.  Mitochondrial dynamics, the ability to move along microtubules and undergo fragmentation (fission) and elongation (fusion), significantly contributes to mitochondrial quality control and elimination of damaged organelles. These processes are well-coordinated in healthy cells, but can go awry in different pathologies, in aging, and in age-related diseases. There is a great deal of information about mitochondrial biology, but there are still a lot of unanswered questions regarding functioning of healthy mitochondria and the mechanisms of mitochondrial dysfunction in aging and age-related pathologies. Consequently, this Special Issue is devoted to new developments in mitochondrial biology and is aimed at elucidating the mechanisms of mitochondrial dysfunction under various pathologies, in healthy aging and age-related diseases.  We invite authors to contribute original research papers as well as review articles. We encourage authors to share their exciting recent findings addressing new developments in mitochondrial biology and clarifying the mechanisms of mitochondrial dysfunction under various conditions.  

Prof. Dr. Nickolay Brustovetsky
Guest Editor

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Keywords

  • mitochondria
  • oxidative phosphorylation
  • mitochondrial ion transport
  • permeability transition pore
  • mitochondrial ROS generation
  • mitochondrial quality control
  • mitochondrial traffic
  • mitochondrial morphology
  • mitochondrial dynamics
  • mitophagy

Published Papers (13 papers)

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Research

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22 pages, 4759 KiB  
Article
Amyloid Beta Oligomers Activate Death Receptors and Mitochondria-Mediated Apoptotic Pathways in Cerebral Vascular Smooth Muscle Cells; Protective Effects of Carbonic Anhydrase Inhibitors
by Amy Anzovino, Elisa Canepa, Micaelly Alves, Nicole L. Lemon, Roxana O. Carare and Silvia Fossati
Cells 2023, 12(24), 2840; https://doi.org/10.3390/cells12242840 - 14 Dec 2023
Cited by 1 | Viewed by 1102
Abstract
Amyloid beta (Aβ) deposition within the brain vasculature is an early hallmark of Alzheimer’s disease (AD), which triggers loss of brain vascular smooth muscle cells (BVSMCs) in cerebral arteries, via poorly understood mechanisms, altering cerebral blood flow, brain waste clearance, and promoting cognitive [...] Read more.
Amyloid beta (Aβ) deposition within the brain vasculature is an early hallmark of Alzheimer’s disease (AD), which triggers loss of brain vascular smooth muscle cells (BVSMCs) in cerebral arteries, via poorly understood mechanisms, altering cerebral blood flow, brain waste clearance, and promoting cognitive impairment. We have previously shown that, in brain endothelial cells (ECs), vasculotropic Aβ species induce apoptosis through death receptors (DRs) DR4 and DR5 and mitochondria-mediated mechanisms, while FDA-approved carbonic anhydrase inhibitors (CAIs) prevent mitochondria-mediated EC apoptosis in vitro and in vivo. In this study, we analyzed Aβ-induced extrinsic and intrinsic (DR- and mitochondria-mediated) apoptotic pathways in BVSMC, aiming to unveil new therapeutic targets to prevent BVSMC stress and death. We show that both apoptotic pathways are activated in BVSMCs by oligomeric Aβ42 and Aβ40-Q22 (AβQ22) and mitochondrial respiration is severely impaired. Importantly, the CAIs methazolamide (MTZ) and acetazolamide (ATZ) prevent the pro-apoptotic effects in BVSMCs, while reducing caspase 3 activation and Aβ deposition in the arterial walls of TgSwDI animals, a murine model of cerebral amyloid angiopathy (CAA). This study reveals new molecular targets and a promising therapeutic strategy against BVSMC dysfunction in AD, CAA, and ARIA (amyloid-related imaging abnormalities) complications of recently FDA-approved anti-Aβ antibodies. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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19 pages, 1924 KiB  
Article
Mitochondrial F-ATP Synthase Co-Migrating Proteins and Ca2+-Dependent Formation of Large Channels
by Anna B. Nikiforova, Yulia L. Baburina, Marina P. Borisova, Alexey K. Surin, Ekaterina S. Kharechkina, Olga V. Krestinina, Maria Y. Suvorina, Svetlana A. Kruglova and Alexey G. Kruglov
Cells 2023, 12(19), 2414; https://doi.org/10.3390/cells12192414 - 07 Oct 2023
Cited by 1 | Viewed by 986
Abstract
Monomers, dimers, and individual FOF1-ATP synthase subunits are, presumably, involved in the formation of the mitochondrial permeability transition pore (PTP), whose molecular structure, however, is still unknown. We hypothesized that, during the Ca2+-dependent assembly of a PTP [...] Read more.
Monomers, dimers, and individual FOF1-ATP synthase subunits are, presumably, involved in the formation of the mitochondrial permeability transition pore (PTP), whose molecular structure, however, is still unknown. We hypothesized that, during the Ca2+-dependent assembly of a PTP complex, the F-ATP synthase (subunits) recruits mitochondrial proteins that do not interact or weakly interact with the F-ATP synthase under normal conditions. Therefore, we examined whether the PTP opening in mitochondria before the separation of supercomplexes via BN-PAGE will increase the channel stability and channel-forming capacity of isolated F-ATP synthase dimers and monomers in planar lipid membranes. Additionally, we studied the specific activity and the protein composition of F-ATP synthase dimers and monomers from rat liver and heart mitochondria before and after PTP opening. Against our expectations, preliminary PTP opening dramatically suppressed the high-conductance channel activity of F-ATP synthase dimers and monomers and decreased their specific “in-gel” activity. The decline in the channel-forming activity correlated with the reduced levels of as few as two proteins in the bands: methylmalonate–semialdehyde dehydrogenase and prohibitin 2. These results indicate that proteins co-migrating with the F-ATP synthase may be important players in PTP formation and stabilization. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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15 pages, 1948 KiB  
Article
The Role of Swelling in the Regulation of OPA1-Mediated Mitochondrial Function in the Heart In Vitro
by Xavier R. Chapa-Dubocq, Keishla M. Rodríguez-Graciani, Jorge García-Báez, Alyssa Vadovsky, Jason N. Bazil and Sabzali Javadov
Cells 2023, 12(16), 2017; https://doi.org/10.3390/cells12162017 - 08 Aug 2023
Viewed by 990
Abstract
Optic atrophy-1 (OPA1) plays a crucial role in the regulation of mitochondria fusion and participates in maintaining the structural integrity of mitochondrial cristae. Here we elucidate the role of OPA1 cleavage induced by calcium swelling in the presence of Myls22 (an OPA1 GTPase [...] Read more.
Optic atrophy-1 (OPA1) plays a crucial role in the regulation of mitochondria fusion and participates in maintaining the structural integrity of mitochondrial cristae. Here we elucidate the role of OPA1 cleavage induced by calcium swelling in the presence of Myls22 (an OPA1 GTPase activity inhibitor) and TPEN (an OMA1 inhibitor). The rate of ADP-stimulated respiration was found diminished by both inhibitors, and they did not prevent Ca2+-induced mitochondrial respiratory dysfunction, membrane depolarization, or swelling. L-OPA1 cleavage was stimulated at state 3 respiration; therefore, our data suggest that L-OPA1 cleavage produces S-OPA1 to maintain mitochondrial bioenergetics in response to stress. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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12 pages, 3757 KiB  
Article
Refractive Index Imaging Reveals That Elimination of the ATP Synthase C Subunit Does Not Prevent the Adenine Nucleotide Translocase-Dependent Mitochondrial Permeability Transition
by Maria A. Neginskaya, Sally E. Morris and Evgeny V. Pavlov
Cells 2023, 12(15), 1950; https://doi.org/10.3390/cells12151950 - 27 Jul 2023
Viewed by 1098
Abstract
The mitochondrial permeability transition pore (mPTP) is a large, weakly selective pore that opens in the mitochondrial inner membrane in response to the pathological increase in matrix Ca2+ concentration. mPTP activation has been implicated as a key factor contributing to stress-induced necrotic [...] Read more.
The mitochondrial permeability transition pore (mPTP) is a large, weakly selective pore that opens in the mitochondrial inner membrane in response to the pathological increase in matrix Ca2+ concentration. mPTP activation has been implicated as a key factor contributing to stress-induced necrotic and apoptotic cell death. The molecular identity of the mPTP is not completely understood. Both ATP synthase and adenine nucleotide translocase (ANT) have been described as important components of the mPTP. Using a refractive index (RI) imaging approach, we recently demonstrated that the removal of either ATP synthase or ANT eliminates the Ca2+-induced mPTP in experiments with intact cells. These results suggest that mPTP formation relies on the interaction between ATP synthase and ANT protein complexes. To gain further insight into this process, we used RI imaging to investigate mPTP properties in cells with a genetically eliminated C subunit of ATP synthase. These cells also lack ATP6, ATP8, 6.8PL subunits and DAPIT but, importantly, have a vestigial ATP synthase complex with assembled F1 and peripheral stalk domains. We found that these cells can still undergo mPTP activation, which can be blocked by the ANT inhibitor bongkrekic acid. These results suggest that ANT can form the pore independently from the C subunit but still requires the presence of other components of ATP synthase. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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0 pages, 5340 KiB  
Article
Rlip Reduction Induces Oxidative Stress and Mitochondrial Dysfunction in Mutant Tau-Expressed Immortalized Hippocampal Neurons: Mechanistic Insights
by P. Hemachandra Reddy, Sudhir Kshirsagar, Chhanda Bose, Jangampalli Adi Pradeepkiran, Ashly Hindle, Sharda P. Singh, Arubala P. Reddy and Javaria Baig
Cells 2023, 12(12), 1646; https://doi.org/10.3390/cells12121646 - 16 Jun 2023
Cited by 3 | Viewed by 1444 | Correction
Abstract
RalBP1 (Rlip) is a stress-activated protein that is believed to play a large role in aging and neurodegenerative diseases such as Alzheimer’s disease (AD) and other tauopathies. The purpose of our study was to understand the role of Rlip in mutant Tau-expressed immortalized [...] Read more.
RalBP1 (Rlip) is a stress-activated protein that is believed to play a large role in aging and neurodegenerative diseases such as Alzheimer’s disease (AD) and other tauopathies. The purpose of our study was to understand the role of Rlip in mutant Tau-expressed immortalized hippocampal HT22 cells. In the current study, we used mutant Tau (mTau)-expressed HT22 neurons and HT22 cells transfected with Rlip-cDNA and/or silenced RNA, and studied the cell survival, mitochondrial respiration, mitochondrial function, immunoblotting, and immunofluorescence analysis of synaptic and mitophagy proteins and the colocalization of Rlip and mTau proteins. We found Rlip protein levels were reduced in mTau-HT22 cells, Rlip silenced HT22 cells, and mTau + Rlip RNA silenced HT22 cells; on the other hand, increased Rlip levels were observed in Rlip cDNA transfected HT22 cells. We found cell survival was decreased in mTau-HT22 cells and RNA-silenced HT22 cells. However, cell survival was increased in Rlip-overexpressed mTau-HT22 cells. A significantly reduced oxygen consumption rate (OCR) was found in mTau-HT22 cells and in RNA-silenced Rlip-HT22 cells, with an even greater reduction in mTau-HT22 + Rlip RNA-silenced HT22 cells. A significantly increased OCR was found in Rlip-overexpressed HT22 cells and in all groups of cells that overexpress Rlip cDNA. Mitochondrial function was defective in mTau-HT22 cells, RNA silenced Rlip in HT22 cells, and was further defective in mTau-HT22 + Rlip RNA-silenced HT22 cells; however, it was rescued in Rlip overexpressed in all groups of HT22 cells. Synaptic and mitophagy proteins were decreased in mTau-HT22 cells, and further reductions were found in RNA-silenced mTau-HT22 cells. However, these were increased in mTau + Rlip-overexpressed HT22 cells. An increased number of mitochondria and decreased mitochondrial length were found in mTau-HT22 cells. These were rescued in Rlip-overexpressed mTau-HT22 cells. These observations strongly suggest that Rlip deficiency causes oxidative stress/mitochondrial dysfunction and Rlip overexpression reverses these defects. Overall, our findings revealed that Rlip is a promising new target for aging, AD, and other tauopathies/neurological diseases. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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16 pages, 4241 KiB  
Article
Mitochondrial Transfer to Host Cells from Ex Vivo Expanded Donor Hematopoietic Stem Cells
by Hiroki Kawano, Yuko Kawano, Chen Yu, Mark W. LaMere, Matthew J. McArthur, Michael W. Becker, Scott W. Ballinger, Satoshi Gojo, Roman A. Eliseev and Laura M. Calvi
Cells 2023, 12(11), 1473; https://doi.org/10.3390/cells12111473 - 25 May 2023
Viewed by 2147
Abstract
Mitochondrial dysfunction is observed in various conditions, from metabolic syndromes to mitochondrial diseases. Moreover, mitochondrial DNA (mtDNA) transfer is an emerging mechanism that enables the restoration of mitochondrial function in damaged cells. Hence, developing a technology that facilitates the transfer of mtDNA can [...] Read more.
Mitochondrial dysfunction is observed in various conditions, from metabolic syndromes to mitochondrial diseases. Moreover, mitochondrial DNA (mtDNA) transfer is an emerging mechanism that enables the restoration of mitochondrial function in damaged cells. Hence, developing a technology that facilitates the transfer of mtDNA can be a promising strategy for the treatment of these conditions. Here, we utilized an ex vivo culture of mouse hematopoietic stem cells (HSCs) and succeeded in expanding the HSCs efficiently. Upon transplantation, sufficient donor HSC engraftment was attained in-host. To assess the mitochondrial transfer via donor HSCs, we used mitochondrial-nuclear exchange (MNX) mice with nuclei from C57BL/6J and mitochondria from the C3H/HeN strain. Cells from MNX mice have C57BL/6J immunophenotype and C3H/HeN mtDNA, which is known to confer a higher stress resistance to mitochondria. Ex vivo expanded MNX HSCs were transplanted into irradiated C57BL/6J mice and the analyses were performed at six weeks post transplantation. We observed high engraftment of the donor cells in the bone marrow. We also found that HSCs from the MNX mice could transfer mtDNA to the host cells. This work highlights the utility of ex vivo expanded HSC to achieve the mitochondrial transfer from donor to host in the transplant setting. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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17 pages, 4267 KiB  
Article
LRP1 Deficiency Promotes Mitostasis in Response to Oxidative Stress: Implications for Mitochondrial Targeting after Traumatic Brain Injury
by Gopal V. Velmurugan, W. Brad Hubbard, Paresh Prajapati, Hemendra J. Vekaria, Samir P. Patel, Alexander G. Rabchevsky and Patrick G. Sullivan
Cells 2023, 12(10), 1445; https://doi.org/10.3390/cells12101445 - 22 May 2023
Cited by 1 | Viewed by 1505
Abstract
The brain undergoes oxidative stress and mitochondrial dysfunction following physiological insults such as Traumatic brain injury (TBI), ischemia-reperfusion, and stroke. Pharmacotherapeutics targeting mitochondria (mitoceuticals) against oxidative stress include antioxidants, mild uncouplers, and enhancers of mitochondrial biogenesis, which have been shown to improve pathophysiological [...] Read more.
The brain undergoes oxidative stress and mitochondrial dysfunction following physiological insults such as Traumatic brain injury (TBI), ischemia-reperfusion, and stroke. Pharmacotherapeutics targeting mitochondria (mitoceuticals) against oxidative stress include antioxidants, mild uncouplers, and enhancers of mitochondrial biogenesis, which have been shown to improve pathophysiological outcomes after TBI. However, to date, there is no effective treatment for TBI. Studies have suggested that the deletion of LDL receptor-related protein 1 (LRP1) in adult neurons or glial cells could be beneficial and promote neuronal health. In this study, we used WT and LRP1 knockout (LKO) mouse embryonic fibroblast cells to examine mitochondrial outcomes following exogenous oxidative stress. Furthermore, we developed a novel technique to measure mitochondrial morphometric dynamics using transgenic mitochondrial reporter mice mtD2g (mitochondrial-specific Dendra2 green) in a TBI model. We found that oxidative stress increased the quantity of fragmented and spherical-shaped mitochondria in the injury core of the ipsilateral cortex following TBI, whereas rod-like elongated mitochondria were seen in the corresponding contralateral cortex. Critically, LRP1 deficiency significantly decreased mitochondrial fragmentation, preserving mitochondrial function and cell growth following exogenous oxidative stress. Collectively, our results show that targeting LRP1 to improve mitochondrial function is a potential pharmacotherapeutic strategy against oxidative damage in TBI and other neurodegenerative diseases. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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25 pages, 4353 KiB  
Article
CRMP2 Participates in Regulating Mitochondrial Morphology and Motility in Alzheimer’s Disease
by Tatiana Brustovetsky, Rajesh Khanna and Nickolay Brustovetsky
Cells 2023, 12(9), 1287; https://doi.org/10.3390/cells12091287 - 29 Apr 2023
Cited by 3 | Viewed by 1732
Abstract
Mitochondrial bioenergetics and dynamics (alterations in morphology and motility of mitochondria) play critical roles in neuronal reactions to varying energy requirements in health and disease. In Alzheimer’s disease (AD), mitochondria undergo excessive fission and become less motile. The mechanisms leading to these alterations [...] Read more.
Mitochondrial bioenergetics and dynamics (alterations in morphology and motility of mitochondria) play critical roles in neuronal reactions to varying energy requirements in health and disease. In Alzheimer’s disease (AD), mitochondria undergo excessive fission and become less motile. The mechanisms leading to these alterations are not completely clear. Here, we show that collapsin response mediator protein 2 (CRMP2) is hyperphosphorylated in AD and that is accompanied by a decreased interaction of CRMP2 with Drp1, Miro 2, and Mitofusin 2, which are proteins involved in regulating mitochondrial morphology and motility. CRMP2 was hyperphosphorylated in postmortem brain tissues of AD patients, in brain lysates, and in cultured cortical neurons from the double transgenic APP/PS1 mice, an AD mouse model. CRMP2 hyperphosphorylation and dissociation from its binding partners correlated with increased Drp1 recruitment to mitochondria, augmented mitochondrial fragmentation, and reduced mitochondrial motility. (S)-lacosamide ((S)-LCM), a small molecule that binds to CRMP2, decreased its phosphorylation at Ser 522 and Thr 509/514, and restored CRMP2′s interaction with Miro 2, Drp1, and Mitofusin 2. This was paralleled by decreased Drp1 recruitment to mitochondria, diminished mitochondrial fragmentation, and improved motility of the organelles. Additionally, (S)-LCM-protected cultured cortical AD neurons from cell death. Thus, our data suggest that CRMP2, in a phosphorylation-dependent manner, participates in the regulation of mitochondrial morphology and motility, and modulates neuronal survival in AD. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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24 pages, 2984 KiB  
Article
Partial Inhibition of Complex I Restores Mitochondrial Morphology and Mitochondria-ER Communication in Hippocampus of APP/PS1 Mice
by Jessica Panes, Thi Kim Oanh Nguyen, Huanyao Gao, Trace A. Christensen, Andrea Stojakovic, Sergey Trushin, Jeffrey L. Salisbury, Jorge Fuentealba and Eugenia Trushina
Cells 2023, 12(8), 1111; https://doi.org/10.3390/cells12081111 - 08 Apr 2023
Cited by 4 | Viewed by 2499
Abstract
Alzheimer’s disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with the small molecule CP2 induces an adaptive stress response, activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, Aβ and pTau accumulation, improved synaptic and mitochondrial [...] Read more.
Alzheimer’s disease (AD) has no cure. Earlier, we showed that partial inhibition of mitochondrial complex I (MCI) with the small molecule CP2 induces an adaptive stress response, activating multiple neuroprotective mechanisms. Chronic treatment reduced inflammation, Aβ and pTau accumulation, improved synaptic and mitochondrial functions, and blocked neurodegeneration in symptomatic APP/PS1 mice, a translational model of AD. Here, using serial block-face scanning electron microscopy (SBFSEM) and three-dimensional (3D) EM reconstructions combined with Western blot analysis and next-generation RNA sequencing, we demonstrate that CP2 treatment also restores mitochondrial morphology and mitochondria-endoplasmic reticulum (ER) communication, reducing ER and unfolded protein response (UPR) stress in the APP/PS1 mouse brain. Using 3D EM volume reconstructions, we show that in the hippocampus of APP/PS1 mice, dendritic mitochondria primarily exist as mitochondria-on-a-string (MOAS). Compared to other morphological phenotypes, MOAS have extensive interaction with the ER membranes, forming multiple mitochondria-ER contact sites (MERCS) known to facilitate abnormal lipid and calcium homeostasis, accumulation of Aβ and pTau, abnormal mitochondrial dynamics, and apoptosis. CP2 treatment reduced MOAS formation, consistent with improved energy homeostasis in the brain, with concomitant reductions in MERCS, ER/UPR stress, and improved lipid homeostasis. These data provide novel information on the MOAS-ER interaction in AD and additional support for the further development of partial MCI inhibitors as a disease-modifying strategy for AD. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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Review

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15 pages, 784 KiB  
Review
Altered Metabolism in Motor Neuron Diseases: Mechanism and Potential Therapeutic Target
by Cassandra Barone and Xin Qi
Cells 2023, 12(11), 1536; https://doi.org/10.3390/cells12111536 - 02 Jun 2023
Cited by 1 | Viewed by 1829
Abstract
Motor Neuron Diseases (MND) are neurological disorders characterized by a loss of varying motor neurons resulting in decreased physical capabilities. Current research is focused on hindering disease progression by determining causes of motor neuron death. Metabolic malfunction has been proposed as a promising [...] Read more.
Motor Neuron Diseases (MND) are neurological disorders characterized by a loss of varying motor neurons resulting in decreased physical capabilities. Current research is focused on hindering disease progression by determining causes of motor neuron death. Metabolic malfunction has been proposed as a promising topic when targeting motor neuron loss. Alterations in metabolism have also been noted at the neuromuscular junction (NMJ) and skeletal muscle tissue, emphasizing the importance of a cohesive system. Finding metabolism changes consistent throughout both neurons and skeletal muscle tissue could pose as a target for therapeutic intervention. This review will focus on metabolic deficits reported in MNDs and propose potential therapeutic targets for future intervention. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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12 pages, 2103 KiB  
Review
Impaired Mitochondrial Function in T-Lymphocytes as a Result of Exposure to HIV and ART
by Alexander V. Blagov, Vasily N. Sukhorukov, Shuzhen Guo, Dongwei Zhang, Mikhail A. Popov and Alexander N. Orekhov
Cells 2023, 12(7), 1072; https://doi.org/10.3390/cells12071072 - 02 Apr 2023
Cited by 2 | Viewed by 1499
Abstract
Mitochondrial dysfunction is a described phenomenon for a number of chronic and infectious diseases. At the same time, the question remains open: is this condition a consequence or a cause of the progression of the disease? In this review, we consider the role [...] Read more.
Mitochondrial dysfunction is a described phenomenon for a number of chronic and infectious diseases. At the same time, the question remains open: is this condition a consequence or a cause of the progression of the disease? In this review, we consider the role of the development of mitochondrial dysfunction in the progression of HIV (human immunodeficiency viruses) infection and the onset of AIDS (acquired immunodeficiency syndrome), as well as the direct impact of HIV on mitochondria. In addition, we will touch upon such an important issue as the effect of ART (Antiretroviral Therapy) drugs on mitochondria, since ART is currently the only effective way to curb the progression of HIV in infected patients, and because the identification of potential side effects can help to more consciously approach the development of new drugs in the treatment of HIV infection. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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Other

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3 pages, 1284 KiB  
Correction
Correction: Reddy et al. Rlip Reduction Induces Oxidative Stress and Mitochondrial Dysfunction in Mutant Tau-Expressed Immortalized Hippocampal Neurons: Mechanistic Insights. Cells 2023, 12, 1646
by P. Hemachandra Reddy, Sudhir Kshirsagar, Chhanda Bose, Jangampalli Adi Pradeepkiran, Ashly Hindle, Sharda P. Singh, Arubala P. Reddy and Javaria Baig
Cells 2024, 13(2), 145; https://doi.org/10.3390/cells13020145 - 12 Jan 2024
Viewed by 499
Abstract
The authors wish to make the following changes to their paper [...] Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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13 pages, 996 KiB  
Opinion
Cellular and Mitochondrial NAD Homeostasis in Health and Disease
by Jaylyn Waddell, Rehana Khatoon and Tibor Kristian
Cells 2023, 12(9), 1329; https://doi.org/10.3390/cells12091329 - 06 May 2023
Cited by 3 | Viewed by 2705
Abstract
The mitochondrion has a unique position among other cellular organelles due to its dynamic properties and symbiotic nature, which is reflected in an active exchange of metabolites and cofactors between the rest of the intracellular compartments. The mitochondrial energy metabolism is greatly dependent [...] Read more.
The mitochondrion has a unique position among other cellular organelles due to its dynamic properties and symbiotic nature, which is reflected in an active exchange of metabolites and cofactors between the rest of the intracellular compartments. The mitochondrial energy metabolism is greatly dependent on nicotinamide adenine dinucleotide (NAD) as a cofactor that is essential for both the activity of respiratory and TCA cycle enzymes. The NAD level is determined by the rate of NAD synthesis, the activity of NAD-consuming enzymes, and the exchange rate between the individual subcellular compartments. In this review, we discuss the NAD synthesis pathways, the NAD degradation enzymes, and NAD subcellular localization, as well as NAD transport mechanisms with a focus on mitochondria. Finally, the effect of the pathologic depletion of mitochondrial NAD pools on mitochondrial proteins’ post-translational modifications and its role in neurodegeneration will be reviewed. Understanding the physiological constraints and mechanisms of NAD maintenance and the exchange between subcellular compartments is critical given NAD’s broad effects and roles in health and disease. Full article
(This article belongs to the Special Issue Mitochondria at the Crossroad of Health and Disease)
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