GLTSCR2/PICT1 links mitochondrial stress and Myc signaling

John Yoon, Alvin J.Y. Ling, Meltem Isik, Dong Young Donna Lee, Michael J. Steinbaugh, Laura M. Sack, Abigail N. Boduch, T. Keith Blackwell, David A. Sinclair, Stephen J. Elledge

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 highthroughput overexpression screen for genes that affect mitochondrial abundance or activity using flow-cytometry-based enrichment of a cell population expressing a high-complexity, concentrationnormalized 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.

Original languageEnglish (US)
Pages (from-to)3781-3786
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number10
DOIs
StatePublished - Mar 11 2014
Externally publishedYes

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Cell Respiration
Mitochondrial Genes
Caenorhabditis elegans
Nuclear Proteins
RNA Interference
Oxygen Consumption
Open Reading Frames
Flow Cytometry
Respiration
Transcription Factors
Maintenance
Cell Proliferation
Population
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Yoon, J., Ling, A. J. Y., Isik, M., Donna Lee, D. Y., Steinbaugh, M. J., Sack, L. M., ... Elledge, S. J. (2014). GLTSCR2/PICT1 links mitochondrial stress and Myc signaling. Proceedings of the National Academy of Sciences of the United States of America, 111(10), 3781-3786. https://doi.org/10.1073/pnas.1400705111

GLTSCR2/PICT1 links mitochondrial stress and Myc signaling. / Yoon, John; Ling, Alvin J.Y.; Isik, Meltem; Donna Lee, Dong Young; Steinbaugh, Michael J.; Sack, Laura M.; Boduch, Abigail N.; Blackwell, T. Keith; Sinclair, David A.; Elledge, Stephen J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 10, 11.03.2014, p. 3781-3786.

Research output: Contribution to journalArticle

Yoon, J, Ling, AJY, Isik, M, Donna Lee, DY, Steinbaugh, MJ, Sack, LM, Boduch, AN, Blackwell, TK, Sinclair, DA & Elledge, SJ 2014, 'GLTSCR2/PICT1 links mitochondrial stress and Myc signaling', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 10, pp. 3781-3786. https://doi.org/10.1073/pnas.1400705111
Yoon, John ; Ling, Alvin J.Y. ; Isik, Meltem ; Donna Lee, Dong Young ; Steinbaugh, Michael J. ; Sack, Laura M. ; Boduch, Abigail N. ; Blackwell, T. Keith ; Sinclair, David A. ; Elledge, Stephen J. / GLTSCR2/PICT1 links mitochondrial stress and Myc signaling. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 10. pp. 3781-3786.
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