Inhibition of human peptide deformylase disrupts mitochondrial function Journal Article
| Authors: | Escobar-Alvarez, S.; Gardner, J.; Sheth, A.; Manfredi, G.; Yang, G.; Ouerfelli, O.; Heaney, M. L.; Scheinberg, D. A. |
| Article Title: | Inhibition of human peptide deformylase disrupts mitochondrial function |
| Abstract: | Deformylases are metalloproteases in bacteria, plants, and humans that remove the N-formyl-methionine off peptides in vitro. The human homolog of peptide deformylase (HsPDF) resides in the mitochondria, along with its putative formylated substrates; however, the cellular function of HsPDF remains elusive. Here we report on the function of HsPDF in mitochondrial translation and oxidative phosphorylation complex biogenesis. Functional HsPDF appears to be necessary for the accumulation of mitochondrial DNA-encoded proteins and assembly of new respiratory complexes containing these proteins. Consequently, inhibition of HsPDF reduces respiratory function and cellular ATP levels, causing dependence on aerobic glycolysis for cell survival. A series of structurally different HsPDF inhibitors and control peptidase inhibitors confirmed that inhibition of HsPDF decreases mtDNA-encoded protein accumulation. Therefore, HsPDF appears to have a role in maintenance of mitochondrial respiratory function, and this function is analogous to that of chloroplast PDF. Copyright © 2010, American Society for Microbiology. All Rights Reserved. |
| Keywords: | controlled study; protein expression; human cell; cell survival; cell function; enzyme inhibition; protein degradation; cell line; enzyme inhibitors; nucleotide sequence; protein biosynthesis; adenosine triphosphate; peptide deformylase; amidohydrolases; dna, mitochondrial; mitochondria; glycolysis; oxidative phosphorylation; biogenesis; mitochondrial dna; mitochondrial respiration; mitochondrial proteins; cytochrome c oxidase; microsomal aminopeptidase; peptide deformylase inhibitor; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone); succinate dehydrogenase (ubiquinone); electron transport chain complex proteins |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 30 |
| Issue: | 21 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 2010-11-01 |
| Start Page: | 5099 |
| End Page: | 5109 |
| Language: | English |
| DOI: | 10.1128/mcb.00469-10 |
| PUBMED: | 20805355 |
| PROVIDER: | scopus |
| PMCID: | PMC2953058 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: MCEBD" - "Source: Scopus" |
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