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J Biol Chem. 2016 Sep 30;291(40):20827-20837. Epub 2016 Aug 5.

Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis.

Author information

1
From the Morgridge Institute for Research, Madison, Wisconsin 53715.
2
the Department of Biomolecular Chemistry and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, Wisconsin 53715, and.
3
From the Morgridge Institute for Research, Madison, Wisconsin 53715, the Department of Biomolecular Chemistry and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, Wisconsin 53715, and.
4
From the Morgridge Institute for Research, Madison, Wisconsin 53715, the Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706 dpagliarini@morgridge.org.

Abstract

Mitochondria are essential organelles that adapt to stress and environmental changes. Among the nutrient signals that affect mitochondrial form and function is iron, whose depletion initiates a rapid and reversible decrease in mitochondrial biogenesis through unclear means. Here we demonstrate that, unlike the canonical iron-induced alterations to transcript stability, loss of iron dampens the transcription of genes encoding mitochondrial proteins with no change to transcript half-life. Using mass spectrometry, we demonstrate that these transcriptional changes are accompanied by dynamic alterations to histone acetylation and methylation levels that are largely reversible upon readministration of iron. Moreover, histone deacetylase inhibition abrogates the decreased histone acetylation observed upon iron deprivation and restores normal transcript levels at genes encoding mitochondrial proteins. Collectively, we demonstrate that deprivation of an essential nutrient induces transcriptional repression of organellar biogenesis involving epigenetic alterations.

KEYWORDS:

MS; histone modification; iron; mitochondria; transcription regulation

PMID:
27497435
PMCID:
PMC5076495
DOI:
10.1074/jbc.M116.727701
[Indexed for MEDLINE]
Free PMC Article

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