Mitochondrial encephalomyopathy in Drosophila.
Mitochondrial encephalomyopathies are common and devastating multisystem genetic disorders characterized by neuromuscular dysfunction and tissue degeneration. Point mutations in the human mitochondrial ATP6 gene are known to cause several related mitochondrial disorders: NARP (neuropathy, ataxia, and retinitis pigmentosa), MILS (maternally inherited Leigh's syndrome), and FBSN (familial bilateral striatal necrosis). We identified a pathogenic mutation in the Drosophila mitochondrial ATP6 gene that causes progressive, adult-onset neuromuscular dysfunction and myodegeneration. Our results demonstrate ultrastructural defects in the mitochondrial innermembrane, neural dysfunction, and a marked reduction in mitochondrial ATP synthase activity associated with this mutation. This Drosophila mutant recapitulates key features of the human neuromuscular disorders enabling detailed in vivo studies of these enigmatic diseases.
Celotto
Alicia M
AM
Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Frank
Adam C
AC
McGrath
Steven W
SW
Fergestad
Tim
T
Van Voorhies
Wayne A
WA
Buttle
Karolyn F
KF
Mannella
Carmen A
CA
Palladino
Michael J
MJ
D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000235:genetics / Q000648:ultrastructure; D005260:Female; D008297:Male; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D017354:Point Mutation
D004272:DNA, Mitochondrial; D029721:Drosophila Proteins; C412204:ATP synthase subunit 6; D025261:Mitochondrial Proton-Translocating ATPases