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Calorie restriction alters mitochondrial protein acetylation
Open accessAbstract
Summary: Calorie restriction (CR) increases lifespan in organisms ranging from budding yeast through mammals. Mitochondrial adaptation represents a key component of the response to CR. Molecular mechanisms underlying this adaptation are largely unknown. Here we show that lysine acetylation of mitochondrial proteins is altered during CR in a tissue‐specific fashion. Via large‐scale mass spectrometry screening, we identify 72 candidate proteins involved in a variety of metabolic pathways with altered acetylation during CR. Mitochondrial acetylation changes may play an important role in the pro‐longevity CR response.
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“Metabolic supplier organs such as the liver and kidney demonstrate mitochondrial hyperacetylation under CR, as does the heart (Schwer et al. 2009); brain mitochondrial acetylation was unchanged, however, and skeletal muscle acetylation decreased.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Schwer et al. 2009
In the citing paper
“Metabolic supplier organs such as the liver and kidney demonstrate mitochondrial hyperacetylation under CR, as does the heart (Schwer et al. 2009); brain mitochondrial acetylation was unchanged, however, and skeletal muscle acetylation decreased.”
From The Mitochondrial Acylome Emerges: Proteomics, Regulation by Sirtuins, and Metabolic and Disease Implications (2018) · cites this paper as Schwer et al. 2009
In the citing paper
“Intriguingly, CR enhances mitochondrial protein acetylation in diverse tissues, such as liver, heart, and kidney (Schwer et al, 2009).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Schwer et al, 2009
In the citing paper
“Additionally, acetylation is regulated by perturbation of energy metabolism as demonstrated by an increase in mitochondrial protein acetylation upon fasting (Kim et al., 2006) and caloric restriction (Schwer et al., 2009) in mice.”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Schwer et al., 2009
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Citations
Cites
Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
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“In mammals, acute fasting and chronic ethanol ingestion also alter hepatic mitochondrial protein acetylation (Kim et al., 2006; Picklo, 2008), suggesting that changes in acetylation represents an ancient, evolutionarily conserved mechanism for adaptation to metabolic ⁄ nutritional stress.”
BackgroundMammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation
Lombard, D. B., Alt, F. W., Cheng, H.-L., Bunkenborg, J., Streeper, R. S., Mostoslavsky, R., Kim, J., Yancopoulos, G., Valenzuela, D., Murphy, A., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01636-07 · Cited by 1,216 · cited 3×
“SIRT4-deficient mice show no gross alterations in hepatic mitochondrial acetylation (Lombard et al., 2007).”
BackgroundInfluentialSelf-citationHaigis, M. C., Mostoslavsky, R., Haigis, K. M., Fahie, K., Christodoulou, D. C., Murphy, A. J., Valenzuela, D. M., Yancopoulos, G. D., Karow, M., Blander, G., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.057 · Cited by 1,162 · cited 1×
“S1) (Haigis et al., 2006; Nakagawa et al., 2009).”
Self-citationImmunoaffinity profiling of tyrosine phosphorylation in cancer cells
Rush, A. J., Moritz, A., Lee, K. A., Guo, A., Goss, V. L., Spek, E. J., Zhang, H., Zha, X., Polakiewicz, R. D., & Comb, M. J. (2004) · Nature Biotechnology · doi:10.1038/nbt1046 · Cited by 1,126 · cited 4×
“Acetylated peptides were subsequently analyzed by mass spectrometry and label-free quantitation (LFQ) (Rush et al., 2005).”
MethodInfluentialSelf-citationSIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
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ResultGrowth Curves and Survival Characteristics of the Animals Used in the Biomarkers of Aging Program
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MethodZhang, J., Sprung, R. W., Pei, J., Tan, X., Kim, S., Zhu, H., Liu, C., Grishin, N. V., & Zhao, Y. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800187-mcp200 · Cited by 474
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“The three mammalian mitochondrial sirtuins – SIRT3, SIRT4, and SIRT5 – are logical candidates to mediate acetylation changes we observe in liver mitochondria in response to CR (Schwer & Verdin, 2008).”
BackgroundSelf-citationCaloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver
Hagopian, K. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00202-4 · Cited by 135 · cited 1×
“Activities of a wide variety of mitochondrial enzymes have been shown to change during CR (Tillman et al., 1996; Dhahbi et al., 2001; Hagopian et al., 2003, 2004, 2005).”
BackgroundHagopian, K., Harper, M., Ram, J. J., Humble, S. J., Weindruch, R. H., & Ramsey, J. J. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00382.2004 · Cited by 106 · cited 1×
“Activities of a wide variety of mitochondrial enzymes have been shown to change during CR (Tillman et al., 1996; Dhahbi et al., 2001; Hagopian et al., 2003, 2004, 2005).”
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“Non-acetylated lysine moieties are positively charged [66], while acetylation of these lysine residues, through a PTM, neutralizes this charge and alters the enzymatic function [67,73].”
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“Because calorie restriction increases SIRT3 expression, the mechanism for increased acetylation in this condition remains unknown.(9,17) An additional Abbreviations: HINT2, histidine triad nucleotide-binding 2.”
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“More recently, work from several groups has demonstrated that lysine acetylation also modulates the activity of several non-histone proteins. in this context, this modification seems particularly abundant on mito chondrial proteins (Schwer et al, 2009).”
BackgroundMitochondrial Regulation by Protein Acetylation
Lombard, D. B., Tishkoff, D. X., & Zwaans, B. M. M. (2012) · Oxidative stress and disease · doi:10.1201/b12308-17 · Cited by 3
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Metadata
- Authors
- Schwer, B., Eckersdorff, M., Li, Y., Silva, J. C., Fermin, D., Kurtev, M. V., Giallourakis, C., Comb, M. J., Alt, F. W., & Lombard, D. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of Michigan (US)
- Cell Signaling Technology (United States) (US)
- Harvard University (US)
- Corresponding author
- Alt, Frederick W.
- Lombard, David B.
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2009-09-24
- Volume
- 8
- Issue
- 5
- Pages
- 604-606
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC2752488
- OpenAlex
- W2095235693
- Cited by
- 259
- References
- 16
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 15 · 2020: 8 · 2019: 15 · 2018: 8 · 2017: 11 · 2016: 24 · 2015: 13 · 2014: 26 · 2013: 37 · 2012: 32
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (AG022325, K08AG022325)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- caloric restriction, mitochondrial protein acetylation, lysine acetylation, mitochondrial adaptation, longevity, lifespan extension, tissue-specific effects, metabolic pathways, aging
- MeSH terms
- Acetylation, Animals, Saccharomycetales, Humans, Life Expectancy, Longevity, Mammals, Mice, Inbred C57BL, Mitochondria, Mitochondria, Liver, Proteins, Caloric Restriction, Mice
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