TY - JOUR
T1 - Complementary RNA and Protein Profiling Identifies Iron as a Key Regulator of Mitochondrial Biogenesis
AU - Rensvold, Jarred W.
AU - Ong, Shao En
AU - Jeevananthan, Athavi
AU - Carr, Steven A.
AU - Mootha, Vamsi K.
AU - Pagliarini, David J.
N1 - Funding Information:
We would like to thank the members of the Eisenstein, Kaplan, V.K.M., and D.J.P. laboratories for helpful discussions and assistance regarding this project. We specifically thank Sarah Calvo and Dan Arlow of the V.K.M. lab for assistance with microarray analyses, Jerry Kaplan and Ivana De Domenico (University of Utah) for providing the ferroportin expression vector, Bruce Spiegelman (Harvard Medical School) for providing the PGC-1α −/− cells, Daniel Kelly (Sanford-Burnham) for providing the PGC-1β f/f/MLC-Cre cells, Randall Johnson and Alex Weidemann (UCSD) for providing the HIF-1α −/− cells, Eric Shoubridge (McGill) for providing the MCH58 cells, and Kelly Werner of the D.J.P. lab for critical reading of the manuscript. This work was supported by a Searle Scholars Award, a Shaw Scientist Award, and USDA Hatch Award WIS01671 (to D.J.P.), NIH R01GM077465 (to V.K.M.), and NIH Molecular Biosciences Training Grant 5T32GM007215-37 (to J.W.R.).
PY - 2013/1/31
Y1 - 2013/1/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84873162025&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2012.11.029
DO - 10.1016/j.celrep.2012.11.029
M3 - Article
C2 - 23318259
AN - SCOPUS:84873162025
SN - 2211-1247
VL - 3
SP - 237
EP - 245
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -