TY - JOUR
T1 - Mitochondrial energy failure in HSD10 disease is due to defective mtDNA transcript processing
AU - Chatfield, Kathryn C.
AU - Coughlin, Curtis R.
AU - Friederich, Marisa W.
AU - Gallagher, Renata C.
AU - Hesselberth, Jay R.
AU - Lovell, Mark A.
AU - Ofman, Rob
AU - Swanson, Michael A.
AU - Thomas, Janet A.
AU - Wanders, Ronald J. A.
AU - Wartchow, Eric P.
AU - van Hove, Johan L. K.
PY - 2015
Y1 - 2015
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.mito.2014.12.005
DO - https://doi.org/10.1016/j.mito.2014.12.005
M3 - Article
C2 - 25575635
SN - 1567-7249
VL - 21
SP - 1
EP - 10
JO - Mitochondrion
JF - Mitochondrion
ER -