title: Complementary RNA and protein profiling identifies iron as a key regulator of mitochondrial biogenesis.
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.
authors: Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors: Jarred W
authors: JW
authors: Rensvold
authors: Shao-En
authors: SE
authors: Ong
authors: Athavi
authors: A
authors: Jeevananthan
authors: Steven A
authors: SA
authors: Carr
authors: Vamsi K
authors: VK
authors: Mootha
authors: David J
authors: DJ
authors: Pagliarini
mesh_terms: D000818:Animals; D019069:Cell Respiration / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D040901:Proteomics; D018075:RNA, Complementary / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D004272:DNA, Mitochondrial; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007502:Iron Chelating Agents; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D018075:RNA, Complementary; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D007501:Iron