Cyclophilin D modulates mitochondrial acetylome

Tiffany Tuyen M Nguyen, Renee Wong, Sara Menazza, Junhui Sun, Yong Chen, Guanghui Wang, Marjan Gucek, Charles Jr Steenbergen, Michael N. Sack, Elizabeth Murphy

Research output: Contribution to journalArticle

Abstract

RATIONALE: Mice lacking cyclophilin D (CypD), a mitochondrial chaperone protein, have altered cardiac metabolism. As acetylation has been shown to regulate metabolism, we tested whether changes in protein acetylation might play a role in these metabolic changes in CypD hearts. OBJECTIVE: Our aim was to test the hypothesis that loss of CypD alters the cardiac mitochondrial acetylome. METHODS AND RESULTS: To identify changes in lysine-acetylated proteins and to map acetylation sites after ablation of CypD, we subjected tryptic digests of isolated cardiac mitochondria from wild-type and CypD mice to immunoprecipitation using agarose beads coupled to antiacetyl lysine antibodies followed by mass spectrometry. We used label-free analysis for the relative quantification of the 875 common peptides that were acetylated in wild-type and CypD samples and found 11 peptides (10 proteins) decreased and 96 peptides (48 proteins) increased in CypD samples. We found increased acetylation of proteins in fatty acid oxidation and branched-chain amino acid metabolism. To evaluate whether this increase in acetylation might play a role in the inhibition of fatty acid oxidation that was previously reported in CypD hearts, we measured the activity of L-3-hydroxyacyl-CoA dehydrogenase, which was acetylated in the CypD hearts. Consistent with the hypothesis, L-3-hydroxyacyl-CoA dehydrogenase activity was inhibited by ≈50% compared with the wild-type mitochondria. CONCLUSIONS: These results implicate a role for CypD in modulating protein acetylation. Taken together, these results suggest that ablation of CypD leads to changes in the mitochondrial acetylome, which may contribute to altered mitochondrial metabolism in CypD mice.

Original languageEnglish (US)
Pages (from-to)1308-1319
Number of pages12
JournalCirculation Research
Volume113
Issue number12
DOIs
StatePublished - Dec 6 2013

Fingerprint

Acetylation
3-Hydroxyacyl-CoA Dehydrogenase
Proteins
Peptides
Lysine
cyclophilin D
Mitochondria
Fatty Acids
Branched Chain Amino Acids
Mitochondrial Proteins
Immunoprecipitation
Sepharose
Mass Spectrometry
Antibodies

Keywords

  • acetylation
  • cyclophilin D
  • mitochondria
  • proteomics
  • sirtuin 3

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nguyen, T. T. M., Wong, R., Menazza, S., Sun, J., Chen, Y., Wang, G., ... Murphy, E. (2013). Cyclophilin D modulates mitochondrial acetylome. Circulation Research, 113(12), 1308-1319. https://doi.org/10.1161/CIRCRESAHA.113.301867

Cyclophilin D modulates mitochondrial acetylome. / Nguyen, Tiffany Tuyen M; Wong, Renee; Menazza, Sara; Sun, Junhui; Chen, Yong; Wang, Guanghui; Gucek, Marjan; Steenbergen, Charles Jr; Sack, Michael N.; Murphy, Elizabeth.

In: Circulation Research, Vol. 113, No. 12, 06.12.2013, p. 1308-1319.

Research output: Contribution to journalArticle

Nguyen, TTM, Wong, R, Menazza, S, Sun, J, Chen, Y, Wang, G, Gucek, M, Steenbergen, CJ, Sack, MN & Murphy, E 2013, 'Cyclophilin D modulates mitochondrial acetylome', Circulation Research, vol. 113, no. 12, pp. 1308-1319. https://doi.org/10.1161/CIRCRESAHA.113.301867
Nguyen TTM, Wong R, Menazza S, Sun J, Chen Y, Wang G et al. Cyclophilin D modulates mitochondrial acetylome. Circulation Research. 2013 Dec 6;113(12):1308-1319. https://doi.org/10.1161/CIRCRESAHA.113.301867
Nguyen, Tiffany Tuyen M ; Wong, Renee ; Menazza, Sara ; Sun, Junhui ; Chen, Yong ; Wang, Guanghui ; Gucek, Marjan ; Steenbergen, Charles Jr ; Sack, Michael N. ; Murphy, Elizabeth. / Cyclophilin D modulates mitochondrial acetylome. In: Circulation Research. 2013 ; Vol. 113, No. 12. pp. 1308-1319.
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AU - Gucek, Marjan

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AU - Sack, Michael N.

AU - Murphy, Elizabeth

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