Journal article
Respiratory chain protein turnover rates in mice are highly heterogeneous but strikingly conserved across tissues, ages, and treatments
The FASEB journal, Vol.29(8), pp.3582-3592
08/2015
DOI: 10.1096/fj.15-272666
PMCID: PMC4511201
PMID: 25977255
Abstract
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.
Details
- Title: Subtitle
- Respiratory chain protein turnover rates in mice are highly heterogeneous but strikingly conserved across tissues, ages, and treatments
- Creators
- Pabalu P Karunadharma - 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, USANathan Basisty - 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, USAYing Ann Chiao - 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, USADao-Fu Dai - 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, USARachel Drake - 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, USANick Levy - 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, USAWilliam J Koh - 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, USAMary J Emond - 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, USAShane Kruse - 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, USADavid Marcinek - 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, USAMichael J Maccoss - 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, USAPeter S Rabinovitch - 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
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.29(8), pp.3582-3592
- Publisher
- United States
- DOI
- 10.1096/fj.15-272666
- PMID
- 25977255
- PMCID
- PMC4511201
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Grant note
- P30 AG0132280 / NIA NIH HHS T32 AG000057 / NIA NIH HHS P30 AG013280 / NIA NIH HHS R01 HL101186 / NHLBI NIH HHS R01 AG038550 / NIA NIH HHS
- Language
- English
- Date published
- 08/2015
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984047887302771
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