Shaping the mitochondrial inner membrane in health and disease

Abstract

Colina-Tenorio L, Horten P, Pfanner N, Rampelt H (University of Freiburg, Freiburg, Germany). Shaping the mitochondrial inner membrane in health and disease (Review Symposium). J Intern Med 2020; 287: 645-664.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 F 1 F o -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.

Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation

“…Mitochondria are the major powerhouses in nearly all cells of the eukaryotic life such as animals including human. Although mitochondria and their associated biomolecules and bioenergetics [1][2][3][4][5][6][7][8] have been studied for more than 50 years, they still remain today as an intriguing research topic of fascinating and unexpected new insights 9 . As illustrated in Fig.…”

Opa1overexpression protects from early onsetMpv17-/--related mouse kidney disease

“…Mitochondrial cristae are controlled by a molecular network formed by the mitochondrial contact site and cristae organizing system (MICOS), the F 1 F o -ATP synthase, the IMM pleiotropic OPA1 protein, and the non-bilayer-forming phospholipids cardiolipin and phosphatidylethanolamine (Colina-Tenorio et al, 2020). OPA1 has been shown to be epistatic to MICOS (Glytsou et al, 2016), and that its protective effect against mitochondrial dysfunction is mediated by ATP synthase oligomerization (Quintana-Cabrera et al, 2018).…”

Cristae Membrane Dynamics – A Paradigm Change

“…All MICOS complex subunits were named as Mic'X' where 'X' represents the molecular weight in kDa [17]. The subunits of the MICOS complex were functionally linked to maintenance of CJs, lipid trafficking, mitochondrial import, and mitochondrial DNA (mtDNA) maintenance [22,23]. Several MICOS subunits are associated with human diseases such as mitochondrial encephalopathy with liver disease, mitochondrial myopathy, neurodegeneration, cognitive impairment, and diabetes, among many others [1,[22][23][24][25][26][27][28][29].…”

“…The subunits of the MICOS complex were functionally linked to maintenance of CJs, lipid trafficking, mitochondrial import, and mitochondrial DNA (mtDNA) maintenance [22,23]. Several MICOS subunits are associated with human diseases such as mitochondrial encephalopathy with liver disease, mitochondrial myopathy, neurodegeneration, cognitive impairment, and diabetes, among many others [1,[22][23][24][25][26][27][28][29]. Mic60 (alternative names mitofilin, HMP, IMMT, Fcj1) was the first subunit discovered, and its depletion led to loss of CJs and the formation of onion ring-like cristae in Saccharomyces cerevisiae (baker's yeast) and mammalian cell lines [21,30].…”