Loss of the Drosophila m-AAA mitochondrial protease paraplegin results in mitochondrial dysfunction, shortened lifespan, and neuronal and muscular degeneration

Cell Death & Disease
Gautam PareekLeo J Pallanck

Abstract

The progressive accumulation of dysfunctional mitochondria is implicated in aging and in common diseases of the elderly. To oppose this occurrence, organisms employ a variety of strategies, including the selective degradation of oxidatively damaged and misfolded mitochondrial proteins. Genetic studies in yeast indicate that the ATPase Associated with diverse cellular Activities (AAA+) family of mitochondrial proteases account for a substantial fraction of this protein degradation, but their metazoan counterparts have been little studied, despite the fact that mutations in the genes encoding these proteases cause a variety of human diseases. To begin to explore the biological roles of the metazoan mitochondrial AAA+ protease family, we have created a CRISPR/Cas9 allele of the Drosophila homolog of SPG7, which encodes an inner membrane-localized AAA+ protease known as paraplegin. Drosophila SPG7 mutants exhibited shortened lifespan, progressive locomotor defects, sensitivity to chemical and environmental stress, and muscular and neuronal degeneration. Ultrastructural examination of photoreceptor neurons indicated that the neurodegenerative phenotype of SPG7 mutants initiates at the synaptic terminal. A variety of mitochondrial de...Continue Reading

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Citations

May 25, 2020·Journal of Neurology·Alma OsmanovicRuthild G Weber
Jul 11, 2018·International Journal of Molecular Sciences·Véronique MonnierJuan Antonio Navarro
Oct 2, 2019·International Journal of Molecular Sciences·Nadezhda V TarasovaAndrey V Elchaninov
Dec 24, 2019·Molecular Aspects of Medicine·Luiz H M BoziJulio C B Ferreira
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Miaolin ZengHaitong Wan

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Methods Mentioned

BETA
proximity ligation
environmental stresses
transmission electron microscopy
confocal microscopy
electrophoresis

Software Mentioned

MitoProt
GraphPad Prism
Basic Local Alignment Search Tool ( BLAST )
Office Excel
KymographBuilder
ImageJ

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