Tags

Type your tag names separated by a space and hit enter

SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage.
Free Radic Biol Med. 2013 Oct; 63:222-34.FR

Abstract

Progressive accumulation of defective mitochondria is a common feature of aged cells. SIRT3 is a NAD(+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. FOXO3 is a direct target of SIRT3 and functions as a forkhead transcription factor to govern diverse cellular responses to stress. Here we show that hydrogen peroxide induces SIRT3 to deacetylate FOXO3 at K271 and K290, followed by the upregulation of a set of genes that are essential for mitochondrial homeostasis (mitochondrial biogenesis, fission/fusion, and mitophagy). Consequently, SIRT3-mediated deacetylation of FOXO3 modulates mitochondrial mass, ATP production, and clearance of defective mitochondria. Thus, mitochondrial quantity and quality are ensured to maintain mitochondrial reserve capacity in response to oxidative damage. Maladaptation to oxidative stress is a major risk factor underlying aging and many aging-related diseases. Hence, our finding that SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative stress provides a possible direction for aging-delaying therapies and disease intervention.

Authors+Show Affiliations

Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, 11221 Taipei, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23665396

Citation

Tseng, Anne H H., et al. "SIRT3 Deacetylates FOXO3 to Protect Mitochondria Against Oxidative Damage." Free Radical Biology & Medicine, vol. 63, 2013, pp. 222-34.
Tseng AH, Shieh SS, Wang DL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med. 2013;63:222-34.
Tseng, A. H., Shieh, S. S., & Wang, D. L. (2013). SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radical Biology & Medicine, 63, 222-34. https://doi.org/10.1016/j.freeradbiomed.2013.05.002
Tseng AH, Shieh SS, Wang DL. SIRT3 Deacetylates FOXO3 to Protect Mitochondria Against Oxidative Damage. Free Radic Biol Med. 2013;63:222-34. PubMed PMID: 23665396.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. AU - Tseng,Anne H H, AU - Shieh,Shyan-Shu, AU - Wang,Danny Ling, Y1 - 2013/05/07/ PY - 2012/12/14/received PY - 2013/05/01/revised PY - 2013/05/01/accepted PY - 2013/5/14/entrez PY - 2013/5/15/pubmed PY - 2013/11/2/medline KW - Aging KW - BAEC KW - CR KW - EC KW - FOXO3 KW - Free radicals KW - HUVEC KW - Mitochondrial biogenesis KW - Mitochondrial fission/fusion KW - Mitochondrial homeostasis KW - Mitophagy KW - OCR KW - Oxidative stress KW - ROS KW - SIRT3 KW - bovine aortic endothelial cell KW - caloric restriction KW - endothelial cell KW - human umbilical vein endothelial cell KW - oxygen consumption rate KW - reactive oxygen species SP - 222 EP - 34 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 63 N2 - Progressive accumulation of defective mitochondria is a common feature of aged cells. SIRT3 is a NAD(+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. FOXO3 is a direct target of SIRT3 and functions as a forkhead transcription factor to govern diverse cellular responses to stress. Here we show that hydrogen peroxide induces SIRT3 to deacetylate FOXO3 at K271 and K290, followed by the upregulation of a set of genes that are essential for mitochondrial homeostasis (mitochondrial biogenesis, fission/fusion, and mitophagy). Consequently, SIRT3-mediated deacetylation of FOXO3 modulates mitochondrial mass, ATP production, and clearance of defective mitochondria. Thus, mitochondrial quantity and quality are ensured to maintain mitochondrial reserve capacity in response to oxidative damage. Maladaptation to oxidative stress is a major risk factor underlying aging and many aging-related diseases. Hence, our finding that SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative stress provides a possible direction for aging-delaying therapies and disease intervention. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/23665396/SIRT3_deacetylates_FOXO3_to_protect_mitochondria_against_oxidative_damage_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(13)00208-6 DB - PRIME DP - Unbound Medicine ER -