A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis.
The human oxidative phosphorylation (OxPhos) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes and serves as the primary cellular pathway for ATP biosynthesis. While the core protein machinery for OxPhos is well characterized, many of its assembly, maturation,...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-08-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000590&type=printable |
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| author | Joshua M Baughman Roland Nilsson Vishal M Gohil Daniel H Arlow Zareen Gauhar Vamsi K Mootha |
| author_facet | Joshua M Baughman Roland Nilsson Vishal M Gohil Daniel H Arlow Zareen Gauhar Vamsi K Mootha |
| author_sort | Joshua M Baughman |
| collection | DOAJ |
| description | The human oxidative phosphorylation (OxPhos) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes and serves as the primary cellular pathway for ATP biosynthesis. While the core protein machinery for OxPhos is well characterized, many of its assembly, maturation, and regulatory factors remain unknown. We exploited the tight transcriptional control of the genes encoding the core OxPhos machinery to identify novel regulators. We developed a computational procedure, which we call expression screening, which integrates information from thousands of microarray data sets in a principled manner to identify genes that are consistently co-expressed with a target pathway across biological contexts. We applied expression screening to predict dozens of novel regulators of OxPhos. For two candidate genes, CHCHD2 and SLIRP, we show that silencing with RNAi results in destabilization of OxPhos complexes and a marked loss of OxPhos enzymatic activity. Moreover, we show that SLIRP plays an essential role in maintaining mitochondrial-localized mRNA transcripts that encode OxPhos protein subunits. Our findings provide a catalogue of potential novel OxPhos regulators that advance our understanding of the coordination between nuclear and mitochondrial genomes for the regulation of cellular energy metabolism. |
| format | Article |
| id | doaj-art-566fc7fd4a704dcd84fd1699d929f3a1 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2009-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-566fc7fd4a704dcd84fd1699d929f3a12025-08-20T03:22:38ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-08-0158e100059010.1371/journal.pgen.1000590A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis.Joshua M BaughmanRoland NilssonVishal M GohilDaniel H ArlowZareen GauharVamsi K MoothaThe human oxidative phosphorylation (OxPhos) system consists of approximately 90 proteins encoded by nuclear and mitochondrial genomes and serves as the primary cellular pathway for ATP biosynthesis. While the core protein machinery for OxPhos is well characterized, many of its assembly, maturation, and regulatory factors remain unknown. We exploited the tight transcriptional control of the genes encoding the core OxPhos machinery to identify novel regulators. We developed a computational procedure, which we call expression screening, which integrates information from thousands of microarray data sets in a principled manner to identify genes that are consistently co-expressed with a target pathway across biological contexts. We applied expression screening to predict dozens of novel regulators of OxPhos. For two candidate genes, CHCHD2 and SLIRP, we show that silencing with RNAi results in destabilization of OxPhos complexes and a marked loss of OxPhos enzymatic activity. Moreover, we show that SLIRP plays an essential role in maintaining mitochondrial-localized mRNA transcripts that encode OxPhos protein subunits. Our findings provide a catalogue of potential novel OxPhos regulators that advance our understanding of the coordination between nuclear and mitochondrial genomes for the regulation of cellular energy metabolism.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000590&type=printable |
| spellingShingle | Joshua M Baughman Roland Nilsson Vishal M Gohil Daniel H Arlow Zareen Gauhar Vamsi K Mootha A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. PLoS Genetics |
| title | A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. |
| title_full | A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. |
| title_fullStr | A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. |
| title_full_unstemmed | A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. |
| title_short | A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis. |
| title_sort | computational screen for regulators of oxidative phosphorylation implicates slirp in mitochondrial rna homeostasis |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000590&type=printable |
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