Dear Colleagues,

Mitochondria are involved in multiple functions in the cell, including energy metabolism, calcium homeostasis, regulation of redox status, and cell death, among others. Thus, the maintenance of mitochondrial homeostasis is critical for cell survival and is tightly regulated by several processes, including mitochondrial biogenesis, mitochondrial dynamics, and mitophagy. This way, the mitochondrial network is continuously restructured while damaged mitochondria are removed, keeping a healthy pool of mitochondria. Mitochondrial dysfunction can occur when one or more of these processes is altered and can ultimately compromise cell metabolism and function. It has been described that mitochondrial dysfunction contributes to several diseases, such as cancer, obesity, or diabetes, and has also been involved in the hallmarks of aging.

This Special Issue, titled “Mitochondrial Metabolism and Function in Health and Disease”, aims to highlight the latest advances in this research topic. We invite authors to submit original research papers and review articles analyzing the contribution of mitochondrial metabolism and function to the development of different pathologies and potential therapeutic strategies to counteract mitochondrial dysfunction.

Prof. Dr. Pilar Roca
Prof. Dr. Jordi Oliver
Dr. Margalida Torrens-Mas
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• mitochondrial function
• mitochondrial metabolism
• mitochondrial biogenesis
• mitophagy
• mitochondrial dynamics
• mitochondrial disease
• cancer
• aging
• obesity

Title: Autophagy regulates mitochondrial activities in cancer
Authors: Vaibhav Jain
Affiliation: Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Abstract: Autophagy is a multistep cellular recycling process that plays a multifaceted role in cancer. By degrading various macromolecules and organelles autophagy produces a variety of nutrients that help tumor growth and metastasis in the advanced stage of cancer. Mitochondria, the powerhouse of a cell produces most of the cellular energy which is consumed for multiple biological functions. In addition to the classical Warburg effect in cancer which generates energy via aerobic glycolysis, the role of mitochondrial derived energy via oxidative phosphorylation is also being appreciated for tumor growth. Recent advancements in autophagy and mitochondrial biology research indicate that the two processes are connected, and this interconnection plays an important role in cancer and other health disorders. This review will discuss how autophagy plays an important role in cancer by maintaining mitochondrial homeostasis and its functional capacities.

Title: 35 Years of TFAM research: Old protein, new puzzles
Authors: Natalya Kozhukhar; Mikhail Alexeyev
Affiliation: University of South Alabama
Abstract: The life of every cell revolves around breaking down food substances (catabolism); harnessing their chemical energy, predominantly in the form of adenosine triphosphate (ATP); and expenditure of this energy on biosynthesis (anabolism) as well as other functions. From this perspective, mitochondria, where the bulk of ATP is produced in most eukaryotic cells, are central to life. Indeed, the impairment of mitochondrial ATP production is associated with severe, progressive, and often lethal mitochondrial disorders for which no cure or effective treatments exist. Mitochondria are also unique among metazoan organelles in that they house their own small genome, i.e., mitochondrial DNA. This genome is critical for oxidative phosphorylation (OXPHOS), the process responsible for producing the majority of cellular ATP in typical metazoan cells. In turn, the maintenance and functioning of the mitochondrial genome critically depend on Transcription Factor A, Mitochondrial (TFAM), whose whole-body ablation is incompatible with life. TFAM is, perhaps, the best-studied mitochondrial protein, yet our understanding of its contributions to mitochondrial biology continues to expand. The current review is intended to summarize our current knowledge of this remarkable protein and highlight some of the existing controversies.

Title: Remodelling of the mitochondrial bioenergetic pathways in human cultured fibroblasts with carbohydrates
Authors: Margherita Protasoni; Jan-Willem Taanman
Affiliation: Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, Royal Free Campus (M12), Rowland Hill Street, London NW3 2PF, United Kingdom
Abstract: Mitochondrial oxidative phosphorylation defects underlie many neurological and neuromuscular diseases. Patients’ primary dermal fibroblasts are one of the most commonly used in vitro models to study mitochondrial pathologies. However, fibroblasts tend to rely more on glycolysis than oxidative phosphorylation for their energy when cultivated in standard high-glucose medium, rendering it difficult to expose mitochondrial dysfunctions. The aim of this study was to systematically investigate to which extent the use of galactose- or fructose-based medium switches the fibroblasts’ energy metabolism to a more oxidative state. Highly proliferative cells depend more on glycolysis than less proliferative cells. Therefore, we investigated two primary dermal fibroblast cultures from healthy subjects: a highly proliferative neonatal culture and a slower growing adult culture. Cells were cultured with 25 mM glucose, galactose or fructose and 4 mM glutamine as carbon sources. Compared to glucose, galactose as well as fructose reduced the cellular proliferation rate but galactose reduced the proliferation rate more than fructose. Both galactose and fructose resulted in a modest increase of mitochondrial content, including mitochondrial DNA, and a disproportionate increase of protein levels, assembly and activity of the oxidative phosphorylation enzyme complexes. Galactose and fructose-based media induce a switch of the prevalent biochemical pathway in cultured fibroblasts, enhancing aerobic metabolism when compared to glucose-based medium. Galactose and fructose stimulate oxidative phosphorylation to a comparable degree but galactose decreases the cellular proliferation rate more than fructose. Therefore, we recommend using fructose-based medium when studying partial oxidative phosphorylation defects in patients’ fibroblasts.