title: The Role of Mitochondrial Non-Enzymatic Protein Acylation in Ageing.
abstract: In recent years, various large-scale proteomic studies have demonstrated that mitochondrial proteins are highly acylated, most commonly by addition of acetyl and succinyl groups. These acyl modifications may be enzyme catalysed but can also be driven non-enzymatically. The latter mechanism is promoted in mitochondria due to the nature of the mitochondrial microenvironment, which is alkaline and contains high concentrations of acyl-CoA species. Protein acylation may modify enzyme activity, typically inhibiting it. We posited that organismal ageing might be accompanied by an accumulation of acylated proteins, especially in mitochondria, and that this might compromise mitochondrial function and contribute to ageing. In this study, we used R. norvegicus, C. elegans and D. melanogaster to compare the acylation status of mitochondrial proteins between young and old animals. We observed a specific age-dependent increase in protein succinylation in worms and flies but not in rat. Rats have two substrate-specific mitochondrial deacylases, SIRT3 and SIRT5 while both flies and worms lack these enzymes. We propose that accumulation of mitochondrial protein acylation contributes to age-dependent mitochondrial functional decline and that SIRT3 and SIRT5 enzymes may promote longevity through regulation of mitochondrial protein acylation during ageing.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Shin Yee
authors.initials: SY
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Li Theng
authors.initials: LT
authors.lastname: Ng
authors.affiliation: Department of Science, Yale- NUS College, Singapore, Singapore.
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Ng
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Science, Yale- NUS College, Singapore, Singapore.|Department of Biological Sciences, National University of Singapore, Singapore.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Tolwinski
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Thilo
authors.initials: T
authors.lastname: Hagen
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Department of Science, Yale- NUS College, Singapore, Singapore.
authors.forename: Jan
authors.initials: J
authors.lastname: Gruber
mesh_terms: D000215:Acylation; D000375:Aging / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D056566:Sirtuin 3 / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D056566:Sirtuin 3; D008239:Lysine