DNAJA3

ATP synthase

Internal medicine

mitochondrial fusion

Enzyme

Mitochondrial DNA

Disease

Membrane

Inner mitochondrial membrane

Biology

Gene

Translocase of the inner membrane

Phosphatidylcholine

Neurodegeneration

Cardiolipin

Phospholipid

Phosphatidylethanolamine

Mitochondrion

Cell biology

Biochemistry

Inner membrane

Medicine

Mitochondrial membrane transport protein

ATP–ADP translocase

FEBS Letters

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.

MICOS and the mitochondrial inner membrane morphology – when things get out of shape