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. 2016 Nov;240(3):253-255.
doi: 10.1002/path.4774. Epub 2016 Sep 29.

In Brief: Mitophagy: mechanisms and role in human disease

Maya Z Springer  1   2 , Kay F Macleod  3   4
Affiliations

In Brief: Mitophagy: mechanisms and role in human disease

Maya Z Springer et al. J Pathol. 2016 Nov.

Abstract

Mitophagy is a selective form of macro-autophagy in which mitochondria are specifically targeted for autophagic degradation. Mitophagy plays an important role in cellular homeostasis by eliminating dysfunctional mitochondria and reducing mitochondrial mass as an adaptive response to stress. Cells execute mitophagy through several non-redundant mechanisms, including the PINK1/Parkin partnership, which modulates turnover of depolarized mitochondria, and stress-induced BNIP3, NIX, and FUNDC1 molecular adaptors, which interact directly with LC3 to promote mitophagy. These pathways are deregulated in human diseases, including cancer, neurodegeneration, metabolic disorders, muscle atrophy, ageing, and inflammation, reflecting the importance of mitophagy as a cellular housekeeping function. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: BNIP3; FUNDC1; NIX; PINK1; Parkin; ageing; autophagy; disease; mitochondria.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Schematic illustrating mechanisms and role of mitophagy in disease
PINK1/Parkin-mediated mitophagy promotes elimination of depolarized mitochondria through the concerted action of PINK1 kinase on ubiquitin and the Parkin E3 ubiquitin ligase that is recruited by PINK1 to the outer mitochondrial membrane where it ubiquitinates substrates such as Mitofusin-2 and VDAC1. The actions of BNIP3 (blu ue) and NIX (red) are induced by stress signals downstream of hypoxia, nutrient deprivation and specific developmental cues. Both BNIP3 and NIX function as homo-dimers at the OMM and interact directly with processed LC3 at phagophore membranes to promote mitochondrial turnover. The interaction of NIX with LC3 and its mitophagy functions are stimulated by interaction with Rheb. Defects in mitophagy contribute to cancer, Parkinson’s disease, ageing and inflammation amongst other diseases as a result of mitochondrial dysfunction, increased ROS production, mtDNA mutation, reduced respiration, altered metabolism and other adverse consequences of the loss of this important mitochondrial quality control mechanism.
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