Respiratory chain protein turnover rates in mice are highly heterogeneous but strikingly conserved across tissues, ages, and treatments.

Autor:	Karunadharma PP; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Basisty N; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Chiao YA; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Dai DF; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Drake R; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Levy N; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Koh WJ; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Emond MJ; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Kruse S; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Marcinek D; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Maccoss MJ; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA., Rabinovitch PS; Department of Pathology, Department of Environmental Health and Biostatistics, Department of Radiology, and Department of Genome Sciences, University of Washington, Seattle, Washington, USA; and The Scripps Research Institute, Jupiter, Florida, USA petersr@u.washington.edu.
Jazyk:	angličtina
Zdroj:	FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2015 Aug; Vol. 29 (8), pp. 3582-92. Date of Electronic Publication: 2015 May 14.
DOI:	10.1096/fj.15-272666
Abstrakt:	The mitochondrial respiratory chain (RC) produces most of the cellular ATP and requires strict quality-control mechanisms. To examine RC subunit proteostasis in vivo, we measured RC protein half-lives (HLs) in mice by liquid chromatography-tandem mass spectrometry with metabolic [(2)H3]-leucine heavy isotope labeling under divergent conditions. We studied 7 tissues/fractions of young and old mice on control diet or one of 2 diet regimens (caloric restriction or rapamycin) that altered protein turnover (42 conditions in total). We observed a 6.5-fold difference in mean HL across tissues and an 11.5-fold difference across all conditions. Normalization to the mean HL of each condition showed that relative HLs were conserved across conditions (Spearman's ρ = 0.57; P < 10(-4)), but were highly heterogeneous between subunits, with a 7.3-fold mean range overall, and a 2.2- to 4.6-fold range within each complex. To identify factors regulating this conserved distribution, we performed statistical analyses to study the correlation of HLs to the properties of the subunits. HLs significantly correlated with localization within the mitochondria, evolutionary origin, location of protein-encoding, and ubiquitination levels. These findings challenge the notion that all subunits in a complex turnover at comparable rates and suggest that there are common rules governing the differential proteolysis of RC protein subunits under divergent cellular conditions. (© FASEB.)
Databáze:	MEDLINE
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