Complementary RNA and Protein Profiling Identifies Iron as a Key Regulator of Mitochondrial Biogenesis

Jarred W. Rensvold, Shao En Ong, Athavi Jeevananthan, Steven A. Carr, Vamsi K. Mootha, David J. Pagliarini

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

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.

Original languageEnglish
Pages (from-to)237-245
Number of pages9
JournalCell Reports
Volume3
Issue number1
DOIs
StatePublished - Jan 31 2013

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