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GLTSCR2/PICT1 links mitochondrial stress and Myc signaling.


ABSTRACT: Mitochondrial defects underlie a multitude of human diseases. Genetic manipulation of mitochondrial regulatory pathways represents a potential therapeutic approach. We have carried out a high-throughput overexpression screen for genes that affect mitochondrial abundance or activity using flow-cytometry-based enrichment of a cell population expressing a high-complexity, concentration-normalized pool of human ORFs. The screen identified 94 candidate mitochondrial regulators including the nuclear protein GLTSCR2, also known as PICT1. GLTSCR2 enhances mitochondrial function and is required for the maintenance of oxygen consumption, consistent with a pivotal role in the control of cellular respiration. RNAi inactivation of the Caenorhabditis elegans ortholog of GLTSCR2 reduces respiration in worms, indicating functional conservation across species. GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc, and is induced by mitochondrial stress, suggesting it may constitute a significant component of the mitochondrial signaling pathway.

SUBMITTER: Yoon JC 

PROVIDER: S-EPMC3956149 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other

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GLTSCR2/PICT1 links mitochondrial stress and Myc signaling.

Yoon John C JC   Ling Alvin J Y AJ   Isik Meltem M   Lee Dong-Young Donna DY   Steinbaugh Michael J MJ   Sack Laura M LM   Boduch Abigail N AN   Blackwell T Keith TK   Sinclair David A DA   Elledge Stephen J SJ  

Proceedings of the National Academy of Sciences of the United States of America 20140220 10


Mitochondrial defects underlie a multitude of human diseases. Genetic manipulation of mitochondrial regulatory pathways represents a potential therapeutic approach. We have carried out a high-throughput overexpression screen for genes that affect mitochondrial abundance or activity using flow-cytometry-based enrichment of a cell population expressing a high-complexity, concentration-normalized pool of human ORFs. The screen identified 94 candidate mitochondrial regulators including the nuclear p  ...[more]

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