Mitochondrial energy failure in HSD10 disease is due to defective mtDNA transcript processing

Mitochondrion. 2015 Mar;21:1-10. doi: 10.1016/j.mito.2014.12.005. Epub 2015 Jan 6.


Muscle, heart and liver were analyzed in a male subject who succumbed to HSD10 disease. Respiratory chain enzyme analysis and BN-PAGE showed reduced activities and assembly of complexes I, III, IV, and V. The mRNAs of all RNase P subunits were preserved in heart and overexpressed in muscle, but MRPP2 protein was severely decreased. RNase P upregulation correlated with increased expression of mitochondrial biogenesis factors and preserved mitochondrial enzymes in muscle, but not in heart where this compensatory mechanism was incomplete. We demonstrate elevated amounts of unprocessed pre-tRNAs and mRNA transcripts encoding mitochondrial subunits indicating deficient RNase P activity. This study provides evidence of abnormal mitochondrial RNA processing causing mitochondrial energy failure in HSD10 disease.

Keywords: HSD10 disease; MHBD disease; MRPP2; RNA processing; RNase P.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism*
  • Acetyl-CoA C-Acetyltransferase / deficiency*
  • Cell Respiration
  • DNA, Mitochondrial / metabolism*
  • Dyskinesias
  • Electron Transport
  • Energy Metabolism*
  • Gene Expression
  • Humans
  • Infant
  • Infant, Newborn
  • Lipid Metabolism, Inborn Errors / physiopathology*
  • Liver / pathology
  • Male
  • Mental Retardation, X-Linked
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • Muscles / pathology
  • Myocardium / pathology
  • RNA Processing, Post-Transcriptional
  • Transcription, Genetic*


  • DNA, Mitochondrial
  • 3-Hydroxyacyl CoA Dehydrogenases
  • HSD17B10 protein, human
  • Acetyl-CoA C-Acetyltransferase

Supplementary concepts

  • Mental Retardation, X-Linked, Syndromic 10