Selective Mitochondrial Autophagy, or Mitophagy

线粒体选择性自噬 综述

REJUVENATION RESEARCHVolume 8, Number 1, 2005© Mary Ann Liebert, Inc.

Perspective

Selective Mitochondrial Autophagy, or Mitophagy, as a

Targeted Defense Against Oxidative Stress,Mitochondrial Dysfunction, and Aging

JOHN J. LEMASTERS

ABSTRACT

In autophagy, portions of cytoplasm are sequestered into autophagosomes and delivered tolysosomes for degradation. Long assumed to be a random process, increasing evidence sug-gests 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 spe-cific outer membrane protein, Uth1p, is required for efficient mitochondrial autophagy. Forthis selective autophagy of mitochondria, we propose the term “mitophagy” to emphasize thenon-random nature of the process. Mitophagy may play a key role in retarding accumulationof somatic mutations of mtDNA with aging.

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NEUKARYOTICCELLS, mitochondria are a key

source of ATP and essential organelles forcell growth and survival in an aerobic envi-ronment. Yet at the same time, mitochondriaare crucial in instigating cell death.1Unlikeother organelles of animal cells, mitochondriaarose from ancient bacteria that developed anendosymbiotic relationship with equally an-cient eukaryotic cells.2Remnants of this bacte-rial origin remain in the mitochondrion’s dou-ble membrane structure, the lack of cholesterolin its inner membrane and its content of bacte-ria-like ribosomes and closed circular DNA. Al-though the size and number of genes encodedby mitochondrial DNA (mtDNA) has de-creased steadily through evolution, mtDNA inhigher vertebrates still encodes 13 proteins es-

sential for the oxidative phosphorylation, themain but hardly only mitochondrial function.Nuclear DNA encodes the remaining 1000 orso mitochondrial proteins, which are synthe-sized by ribosomes in the cytosol.

A side product of mitochondrial respiratoryactivity is formation of reactive oxygen species(ROS) such as superoxide, hydrogen peroxide,and hydroxyl radical. ROS attack proteins,lipids and nucleic acids and initiate peroxida-tion chain reactions. Perhaps as a consequenceof this rough duty, mitochondria turn over con-stantly to be replaced every 10–25 days, evenin tissues with little or no cellular proliferation,such as brain, heart, liver, and kidney.3Newmitochondria arise by binary fission of pre-ex-isting mitochondria, much like bacteria, and

Department of Cell and Developmental Biology, School of Medicine, University of North Carolina, Chapel Hill,North Carolina.

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