Evidence for selective mitochondrial autophagy and failure in aging.
Autophagy is a major intracellular degradation/recycling system ubiquitous in eukaryotic cells. It contributes to the turnover of cellular components by delivering portions of the cytoplasm and organelles to lysosomes, where they are digested. Starvation-induced autophagy is required for maintaining an amino acid pool for gluconeogenesis and for the synthesis of proteins essential to survival under starvation conditions. In addition, autophagy plays an important role in the degradation of excess or injured organelles, including mitochondria. To test the hypothesis of an involvement of a decrease in autophagy in the process of aging, we explored the antiaging effects of pharmacological stimulation of autophagy on the age-dependent accumulation of 8-OHdG-rich mitochondria in rat liver. Male 3-month and 16-month-old 24 hours-fasted Sprague Dawley rats were injected with the antilipolytic agent [3,5-dimethylpyrazole (DMP)] intraperitoneally. Results showed that drug injection rescued older cells from the accumulation of 8-OHdG in the mtDNA in less than 6 hours, but no significant decrease in the level of cytochrome c oxidase activity was observed. Together, these data provide indirect evidence that 8-OHdG might accumulate in a small pool of mitochondria with increasing age rather than be degraded by the autophagic machinery selectively.
Cavallini
Gabriella
G
Centro di Ricerca di Biologia e Patologia dell'Invecchiamento, Università di Pisa, Via Roma 55, Pisa 56126, Italy.
Donati
Alessio
A
Taddei
Michele
M
Bergamini
Ettore
E
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D031204:Caloric Restriction; D045304:Cytochromes c / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004272:DNA, Mitochondrial; D011720:Pyrazoles; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045304:Cytochromes c; D003849:Deoxyguanosine; C027635:3,5-dimethylpyrazole