PXD009110

PXD009110 is an original dataset announced via ProteomeXchange.

Title	SIRT3 Deacetylates TFAM to Promote Mitochondrial Biogenesis
Description	SIRT3 is a NAD+-dependent mitochondrial protein deacetylase participating in the regulation of central metabolism and mitochondrial proteostasis. SIRT3 is downregulated in clear cell renal cell carcinoma (ccRCC), a main type of renal cancers, but the function of SIRT3 in tumorigenesis and development of ccRCC remains unknown. In this study, we established a SIRT3 overexpressed cell line to explore the changes of proteomics and metabolomics regulated by SIRT3 expression. Both the results of quantitative proteomics, metabolomics and acetylome showed overexpression of SIRT3 increased mitochondrial biogenesis and reversed the mitochondrial dysfunctions in ccRCC. We found SIRT3 could increase the activity of TFAM through modulation of TFAM transcription, degradation and acetylation level. The acetylation of TFAM K154 decreased while TFAM protein expression increased after SIRT3 overexpression. Further study revealed that SIRT3 could bind with TFAM, and decrease the acetylation of TFAM, promoting TFAM activity in mitochondrial biogenesis. Overall, our results present a new mechanism of SIRT3 in regulating mitochondrial functions, and the downregulation of SIRT3 in ccRCC lowers the activity of TFAM, subsequently inhibits the transcription of mitochondrial genes and mitochondrial biogenesis.
HostingRepository	PRIDE
AnnounceDate	2018-08-14
AnnouncementXML	Submission_2018-08-14_09:17:27.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuling Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; 6x(13)C labeled residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-05 04:29:39	ID requested
⏵ 1	2018-08-14 09:17:29	announced

Liu H, Li S, Liu X, Chen Y, Deng H, SIRT3 Overexpression Inhibits Growth of Kidney Tumor Cells and Enhances Mitochondrial Biogenesis. J Proteome Res, 17(9):3143-3152(2018) [pubmed]

curator keyword: Biological

submitter keyword: clear cell renal cancer, SIRT3, proteomics, mitochondrial biogenesis, TFAM acetylation

Huan Liu
contact affiliation	School of Life Sciences,Tsinghua University
contact email	965428084@qq.com
lab head
Yuling Chen
contact affiliation	Tsinghua University
contact email	chenyuling2010@yeah.net
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD009110
     1. Label: PRIDE project
     2. Name: SIRT3 Deacetylates TFAM to Promote Mitochondrial Biogenesis