Mitochondrial dynamics: Biological roles, molecular machinery, and related diseases

Abstract

Mitochondria are dynamic organelles that undergo fusion, fission, movement, and mitophagy. These processes are essential to maintain the normal mitochondrial morphology, distribution, and function. Mitochondrial fusion allows the exchange of intramitochondrial material, whereas the fission process is required to replicate the mitochondria during cell division, facilitate the transport and distribution of mitochondria, and allow the isolation of damaged organelles. Mitochondrial mobility is essential for mitochondrial distribution depending on the cellular metabolic demands. Mitophagy is needed for the elimination of dysfunctional and damaged mitochondria to maintain a healthy mitochondrial population. The mitochondrial dynamic processes are mediated by a number of nuclear-encoded proteins that function in mitochondrial transport, fusion, fission, and mitophagy. Disorders of mitochondrial dynamics are caused by pathogenic variants in the genes encoding these proteins. These diseases have a high clinical variability, and range in severity from isolated optic atrophy to lethal encephalopathy. These disorders include defects in mitochondrial fusion (caused by pathogenic variants in MFN2, OPA1, YME1L1, MSTO1, and FBXL4), mitochondrial fission (caused by pathogenic variants in DNM1L and MFF), and mitochondrial autophagy (caused by pathogenic variants in PINK1 and PRKN). In this review, the molecular machinery and biological roles of mitochondrial dynamic processes are discussed. Subsequently, the currently known diseases related to mitochondrial dynamic defects are presented.

Keywords: DNM1L; FBXL4; MFF; MFN2; MSTO1; Mitochondrial fission; Mitochondrial fusion; Mitophagy; OPA1; PINK1; PRKN; YME1L1.