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MICOS and the mitochondrial inner membrane morphology – when things get out of shape
Author(s) -
Mukherjee Indrani,
Ghosh Mausumi,
Meinecke Michael
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14089
Subject(s) - cardiolipin , phosphatidylethanolamine , microbiology and biotechnology , inner membrane , inner mitochondrial membrane , mitochondrion , translocase of the inner membrane , atp–adp translocase , biology , neurodegeneration , dnaja3 , atp synthase , mitochondrial fusion , translocase of the outer membrane , mitophagy , biochemistry , mitochondrial membrane transport protein , apoptosis , autophagy , phospholipid , membrane , mitochondrial dna , medicine , enzyme , disease , gene , phosphatidylcholine
Mitochondria play a key role in cellular signalling, metabolism and energetics. Proper architecture and remodelling of the inner mitochondrial membrane are essential for efficient respiration, apoptosis and quality control in the cell. Several protein complexes including mitochondrial contact site and cristae organizing system (MICOS), F 1 F O ‐ATP synthase, and Optic Atrophy 1 (OPA1), facilitate formation, maintenance and stability of cristae membranes. MICOS, the F 1 F O ‐ATP synthase, OPA1 and inner membrane phospholipids such as cardiolipin and phosphatidylethanolamine interact with each other to organize the inner membrane ultra‐structure and remodel cristae in response to the cell's demands. Functional alterations in these proteins or in the biosynthesis pathway of cardiolipin and phosphatidylethanolamine result in an aberrant inner membrane architecture and impair mitochondrial function. Mitochondrial dysfunction and abnormalities hallmark several human conditions and diseases including neurodegeneration, cardiomyopathies and diabetes mellitus. Yet, they have long been regarded as secondary pathological effects. This review discusses emerging evidence of a direct relationship between protein‐ and lipid‐dependent regulation of the inner mitochondrial membrane morphology and diseases such as fatal encephalopathy, Leigh syndrome, Parkinson's disease, and cancer.