Proteins and Protein-Complexes Underlying Mitochondrial Structure-Function and Metabolism: Implications in Diseases

Most proteins do not function alone but coordinate as part of multiprotein complexes involved in diverse structural and functional roles within the cell. The best example of this is the mitochondrial electron transport system (ETS). The ETS is involved in the sequential transfer of electrons through different proteins in various protein complexes facilitating the generation of a proton gradient coupled to the synthesis of ATP, the energy currency in a cell. The current concept of mitochondrial architecture states that the ETS associated protein complexes are not randomly distributed within the inner mitochondrial membrane, but assemble into supramolecular structures. For example, the majority of Complex-I is found bound with a Complex-III dimer and Complex-IV, a structure that contains all complexes required to pass electrons from NADH to O2. This is known as a respirasome and its structure is key to rapid and efficient electron transfer during oxidative phosphorylation.

Whilst our understanding of individual protein function in the mitochondria has expanded, research on protein function in the context of multiprotein complexes is still lacking, particularly their roles in metabolism, maintaining a mitochondrial structure-function relationship and their influence in pathogenesis of diseases. Past studies have focused on the relative abundance of ETS-associated proteins and correlated that to mitochondrial functional abnormalities. However, the relative abundance of supramolecular complexes in the mitochondria under diseased conditions, their functional relevance, and the factors underlying their dyshomeostasis have not yet been well studied. In addition to the ETS-associated supramolecular complexes, there is also a growing need to focus research on less explored protein complexes, for example, protein complexes that form between the mitochondrial outer membrane and inner membrane which regulates the intra-mitochondrial transport of proteins, lipids, and metabolites from the cytosol. This will help in understanding the mitochondrial structure-function relationship in the context of health and disease.

Therefore, this research topic encourages submissions that shed light on all of the above-mentioned aspects of mitochondrial functioning to advance knowledge in the field. We welcome contributions in the form of research articles, reviews, mini-reviews, or perspectives that cover but are not limited to, the following topics:
- Mitochondrial protein complexes and their role in structure and function.
- Membrane receptor-mediated signal transductions and regulation of mitochondrial protein
complexes and function.
- Altered mitochondrial proteins and/or protein complexes in diseases: functional implications.
- Novel tools to study mitochondrial proteins and protein complexes as well as metabolic function.
-Comparative analysis of mitochondrial structure and function in different spectrums of
metabolism diseases.
- Biomarkers to identify mitochondrial malfunction in metabolic diseases.
- Regulation of mitochondrial function by cytosolic proteins.
- Role of the cytoskeleton in regulating the structural organization and function of the
mitochondria.
- Molecular basis of the cell-type-specific regulation of mitochondrial function.
- Comparative cell/tissue-type-specific analysis of mitochondrial structure and function.

Note: Topic Editor Mohammad Golam Sabbir is the co-founder and CSO of Alzo Biosciences Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.