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 language | English (US) |
|---|---|
| Pages (from-to) | 3781-3786 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 111 |
| Issue number | 10 |
| DOIs | |
| State | Published - Mar 11 2014 |
| Externally published | Yes |
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ASJC Scopus subject areas
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Cite this
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 journal › Article
}
TY - JOUR
T1 - GLTSCR2/PICT1 links mitochondrial stress and Myc signaling
AU - Yoon, John
AU - Ling, Alvin J.Y.
AU - Isik, Meltem
AU - Donna Lee, Dong Young
AU - Steinbaugh, Michael J.
AU - Sack, Laura M.
AU - Boduch, Abigail N.
AU - Blackwell, T. Keith
AU - Sinclair, David A.
AU - Elledge, Stephen J.
PY - 2014/3/11
Y1 - 2014/3/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84896291761&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896291761&partnerID=8YFLogxK
U2 - 10.1073/pnas.1400705111
DO - 10.1073/pnas.1400705111
M3 - Article
C2 - 24556985
AN - SCOPUS:84896291761
VL - 111
SP - 3781
EP - 3786
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 10
ER -