You are here

Cell Rep DOI:10.1016/j.celrep.2012.11.029

Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.

Publication TypeJournal Article
Year of Publication2013
AuthorsRensvold, JW, Ong, S-E, Jeevananthan, A, Carr, SA, Mootha, VK, Pagliarini, DJ
JournalCell Rep
Volume3
Issue1
Pages237-45
Date Published2013 Jan 31
ISSN2211-1247
KeywordsAnimals, Cell Respiration, DNA, Mitochondrial, Gene Expression Regulation, HEK293 Cells, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Iron, Iron Chelating Agents, Mice, Mitochondrial Proteins, Mitochondrial Turnover, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Proteomics, Rats, RNA, Complementary, RNA, Messenger, Time Factors, Trans-Activators, Transcription Factors
Abstract

Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative data sets that can be leveraged to explore posttranscriptional and posttranslational processes that are essential for mitochondrial adaptation.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S2211-1247(12)00456-1
DOI10.1016/j.celrep.2012.11.029
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23318259?dopt=Abstract

Alternate JournalCell Rep
PubMed ID23318259
PubMed Central IDPMC3812070
Grant ListR01 GM077465 / GM / NIGMS NIH HHS / United States
T32 GM007215 / GM / NIGMS NIH HHS / United States
5T32GM007215-37 / GM / NIGMS NIH HHS / United States
R01GM077465 / GM / NIGMS NIH HHS / United States