Selective Mitochondrial Autophagy, or Mitophagy, as a Targeted Defense Against Oxidative Stress, Mitochondrial Dysfunction, and Aging

TLDR

Autophagy sequesters cytoplasmic material into autophagosomes for lysosomal degradation, and recent evidence indicates that this process is selective for mitochondria, peroxisomes, and other organelles, as shown by the requirement of the outer membrane protein Uth1p in yeast. The authors propose the term “mitophagy” to describe this selective, non‑random mitochondrial autophagy. Mitophagy is defined as the targeted degradation of mitochondria via autophagosomes, distinguishing it from bulk autophagy. Yeast experiments demonstrate that Uth1p is essential for efficient mitophagy, and the process may reduce somatic mtDNA mutation accumulation during aging.

Abstract

In autophagy, portions of cytoplasm are sequestered into autophagosomes and delivered to lysosomes for degradation. Long assumed to be a random process, increasing evidence suggests that autophagy of mitochondria, peroxisomes, and possibly other organelles is selective. A recent paper (Kissova et al., J. Biol. Chem. 2004;279:39068-39074) shows in yeast that a specific outer membrane protein, Uth1p, is required for efficient mitochondrial autophagy. For this selective autophagy of mitochondria, we propose the term "mitophagy" to emphasize the non-random nature of the process. Mitophagy may play a key role in retarding accumulation of somatic mutations of mtDNA with aging.