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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MSK Authors
  1. Mark L Heaney
    94 Heaney
  2. Ouathek Ouerfelli
    102 Ouerfelli
  3. Guangli Yang
    34 Yang
  4. Jeffrey Gardner
    34 Gardner
  5. Aneesh Sheth
    5 Sheth