Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants

• DOI: 10.1073/pnas.0737556100
• Publication Date: 2003-04-01T19:25:08Z
• Authors: Jessica C. Greene; Alexander J. Whit...; Isabella Kuo; Laurie A. Andrews; Mel B. Feany; Leo J. Pallanck
• Keywords: Male; 0301 basic medicine; 0303 health sciences; Sequence Homology, Amino Acid; Ubiquitin-Protein Ligases; Longevity; Molecular Sequence Data; Apoptosis; Parkinson Disease; Spermatids; Recombinant Proteins; Mitochondria; Ligases; 03 medical and health sciences; Mutagenesis; Nerve Degeneration; Animals; Drosophila; Amino Acid Sequence; Cloning, Molecular; Muscle, Skeletal; Sequence Alignment

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Several lines evidence strongly implicate mitochondrial dysfunction as major causative factor PD, although molecular mechanisms responsible for are poorly understood. Recently, loss-of-function mutations parkin gene, which encodes ubiquitin-protein ligase, were found to underlie familial form PD known autosomal recessive juvenile parkinsonism (AR-JP). To gain insight into mechanism selective cell death AR-JP, we have created Drosophila model this disorder. null mutants exhibit reduced lifespan, locomotor defects, and male sterility. The defects derive from apoptotic muscle subsets, whereas sterile phenotype derives spermatid individualization defect at late stage spermatogenesis. Mitochondrial pathology earliest manifestation degeneration prominent characteristic individualizing spermatids mutants. These results indicate that tissue-specific phenotypes observed result raise possibility similar impairment triggers AR-JP.