Research ResourceCell Biology

A Systems Approach for Decoding Mitochondrial Retrograde Signaling Pathways

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Science Signaling  26 Feb 2013:
Vol. 6, Issue 264, pp. rs4
DOI: 10.1126/scisignal.2003266

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Signaling Mitochondrial Dysfunction

The mitochondrial and nuclear genomes contribute to mitochondrial function, and when mitochondrial function is compromised, mitochondrial retrograde signaling alters nuclear gene expression. Chae et al. performed gene expression profiling of engineered cells that had mitochondria containing a disease-associated mutation that causes mitochondrial dysfunction. By generating networks of transcription factors that targeted these genes, the authors revealed putative mitochondrial retrograde signaling pathways. One such pathway involved retinoic X receptor α (RXRA), the mRNA for which was reduced in the mutant cells. Network analysis and experiments in cells suggested that mitochondrial dysfunction caused by the mutation initiated a positive feedback loop that aggravated mitochondrial dysfunction: Reduced RXRA abundance further compromised expression of genes encoding products involved in mitochondrial function and translation. This gene transcription factor mapping network approach may reveal targets for therapeutic intervention of diseases associated with mitochondrial dysfunction.

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