Mitochondria-ER Contact Sites as a Platform Determining Cell Fate and Regulating Metabolism

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

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 1150

Special Issue Editors

Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland
Interests: mitochondrial metabolism; oxidative stress; organelles interactions; metabolic diseases
Department of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Ferrara, Italy
Interests: cancer; cancer biology; inflammation; mitochondria; endoplasmic reticulum; NLRP3 inflammasome; signal transduction; cell signaling
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Special Issue Information

Dear Colleagues,

Research carried out by many laboratories in recent years has focused on the physical interaction between the endoplasmic reticulum (ER) and mitochondria. These two organelles form specific membranous domains termed mitochondria–ER contact sites (MERCs) or mitochondria-associated membranes (MAMs), endowed with specialized proteomic machinery that provides a platform for signalling pathways regulating different processes, which is crucial for proper cell functioning and can even decide cell fate. The role played by mitochondria–ER contact sites ranges from phospholipid synthesis and transfer in the cell, to the coordination of calcium homeostasis, autophagy, and apoptosis, as well as the regulation of inflammation and immune responses.

Moreover, since mitochondria are the organelles where the energy metabolism meets the redox homeostasis, the correct communication between ER and mitochondria and ER-derived signals are the key regulators of mitochondrial metabolism and redox balance. Interactions between mitochondria and ER will therefore play a significant role in the response to both extracellular and intracellular physiological or stress stimuli. A growing body of evidence shows that disturbances of mechanistic or/and functional interactions between ER and mitochondria affect the cell physiology and, consequently, the entire organism. For this reason, disturbances in the communication between the mitochondria and ER are studied in cancer, neurodegenerative and metabolic diseases and many other pathologies. It is extremely important to make every effort to investigate and describe the mechanisms and signalling pathways which involve the interactions of ER and mitochondria. Such knowledge may help to understand the role of these relationships in the proper functioning of the cell and the entire organism.

The aim of this Special Issue is to collect the latest reports on the role of the interactions between the ER and mitochondria in physiology and pathology, with particular emphasis on the redox homeostasis and metabolism regulation in which ER–mitochondria contact sites are involved. This Cells Special Issue welcomes original research articles and review articles describing the regulatory mechanisms at the ER–mitochondria interface and ER–mitochondria contact sites’ role in multiple functions in various scientific biological models.

We look forward to receiving your contributions.

Dr. Magdalena Lebiedzinska-Arciszewska
Dr. Sonia Missiroli
Guest Editors

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  • mitochondria
  • endoplasmic reticulum
  • ER–mitochondria contact sites
  • mitochondria associated membranes
  • oxidative stress
  • redox homeostasis
  • calcium signalling
  • inflammation
  • metabolism
  • apoptosis

Published Papers (1 paper)

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20 pages, 4240 KiB  
The Complex Effects of PKM2 and PKM2:IP3R Disruption on Intracellular Ca2+ Handling and Cellular Functions
Cells 2023, 12(21), 2527; - 26 Oct 2023
Viewed by 937
Pyruvate kinase M (PKM) 2 was described to interact with the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and suppress its activity. To further investigate the physiological importance of the PKM2:IP3R interaction, we developed and characterized HeLa PKM2 knockout [...] Read more.
Pyruvate kinase M (PKM) 2 was described to interact with the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and suppress its activity. To further investigate the physiological importance of the PKM2:IP3R interaction, we developed and characterized HeLa PKM2 knockout (KO) cells. In the HeLa PKM2 KO cells, the release of Ca2+ to the cytosol appears to be more sensitive to low agonist concentrations than in HeLa wild-type (WT) cells. However, upon an identical IP3-induced Ca2+ release, Ca2+ uptake in the mitochondria is decreased in HeLa PKM2 KO cells, which may be explained by the smaller number of contact sites between the ER and the mitochondria. Furthermore, in HeLa PKM2 KO cells, mitochondria are more numerous, though they are smaller and less branched and have a hyperpolarized membrane potential. TAT-D5SD, a cell-permeable peptide representing a sequence derived from IP3R1 that can disrupt the PKM2:IP3R interaction, induces Ca2+ release into the cytosol and Ca2+ uptake into mitochondria in both HeLa WT and PKM2 KO cells. Moreover, TAT-D5SD induced apoptosis in HeLa WT and PKM2 KO cells but not in HeLa cells completely devoid of IP3Rs. These results indicate that PKM2 separately regulates cytosolic and mitochondrial Ca2+ handling and that the cytotoxic effect of TAT-D5SD depends on IP3R activity but not on PKM2. However, the tyrosine kinase Lck, which also interacts with the D5SD sequence, is expressed neither in HeLa WT nor PKM2 KO cells, and we can also exclude a role for PKM1, which is upregulated in HeLa PKM2 KO cells, indicating that the TAT-D5SD peptide has a more complex mode of action than anticipated. Full article
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