Shaping the mitochondrial inner membrane in health and disease

J Intern Med. 2020 Jun;287(6):645-664. doi: 10.1111/joim.13031. Epub 2020 Feb 26.

Abstract

Mitochondria play central roles in cellular energetics, metabolism and signalling. Efficient respiration, mitochondrial quality control, apoptosis and inheritance of mitochondrial DNA depend on the proper architecture of the mitochondrial membranes and a dynamic remodelling of inner membrane cristae. Defects in mitochondrial architecture can result in severe human diseases affecting predominantly the nervous system and the heart. Inner membrane morphology is generated and maintained in particular by the mitochondrial contact site and cristae organizing system (MICOS), the F1 Fo -ATP synthase, the fusion protein OPA1/Mgm1 and the nonbilayer-forming phospholipids cardiolipin and phosphatidylethanolamine. These protein complexes and phospholipids are embedded in a network of functional interactions. They communicate with each other and additional factors, enabling them to balance different aspects of cristae biogenesis and to dynamically remodel the inner mitochondrial membrane. Genetic alterations disturbing these membrane-shaping factors can lead to human pathologies including fatal encephalopathy, dominant optic atrophy, Leigh syndrome, Parkinson's disease and Barth syndrome.

Keywords: MICOS; cristae membranes; human disease; mitochondria; mitochondriopathies; oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA, Mitochondrial / genetics
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Mitochondria / ultrastructure
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Membranes / metabolism*
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Mitochondrial Proton-Translocating ATPases / metabolism
  • Mutation / genetics

Substances

  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • Mitochondrial Proton-Translocating ATPases