title: Loss of NAD-Dependent Protein Deacetylase Sirtuin-2 Alters Mitochondrial Protein Acetylation and Dysregulates Mitophagy.
abstract: Sirtuins connect energy generation and metabolic stress to the cellular acetylome. Currently, only the mitochondrial sirtuins (SIRT3-5) and SIRT1 have been shown to direct mitochondrial function; however, Aims: NAD-dependent protein deacetylase sirtuin-2 (SIRT2), the primary cytoplasmic sirtuin, is not yet reported to associate with mitochondria.
  
  
  
  This study revealed a novel physiological function of SIRT2: the regulation of mitochondrial function. First, the acetylation of several metabolic mitochondrial proteins was found to be altered in Sirt2-deficient mice, which was, subsequently, validated by immunoprecipitation experiments in which the acetylated mitochondrial proteins directly interacted with SIRT2. Moreover, immuno-gold electron microscopic images of mouse brains showed that SIRT2 associates with the inner mitochondrial membrane in central nervous system cells. The loss of Sirt2 increased oxidative stress, decreased adenosine triphosphate levels, and altered mitochondrial morphology at the cellular and tissue (i.e., brain) level. Furthermore, the autophagic/mitophagic processes were dysregulated in Sirt2-deficient neurons and mouse embryonic fibroblasts.
  
  
  
  For the first time it is shown that SIRT2 directs mitochondrial metabolism.
  
  
  
  Together, these findings support that SIRT2 functions as a mitochondrial sirtuin, as well as a regulator of autophagy/mitophagy to maintain mitochondrial biology, thus facilitating cell survival. Antioxid. Redox Signal. 26, 849-863.
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Liu
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Marta
authors.initials: M
authors.lastname: Imbesi
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: William Joseph
authors.initials: WJ
authors.lastname: Nathan
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.|2 Driskill Graduate Program of Life Sciences, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Zou
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: Loukia
authors.initials: L
authors.lastname: Parisiadou
authors.affiliation: 1 Department of Radiation Oncology, Robert Lurie Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors.forename: David
authors.initials: D
authors.lastname: Gius
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063306:Mitophagy; D056565:Sirtuin 2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; C474199:SIRT2 protein, human; D056565:Sirtuin 2
keywords: ROS; SIRT2; autophagy; metabolism; mitochondria; mitophagy; sirtuins