Reduction of endoplasmic reticulum stress attenuates the defects caused by Drosophila mitofusin depletion.
Ablation of the mitochondrial fusion and endoplasmic reticulum (ER)-tethering protein Mfn2 causes ER stress, but whether this is just an epiphenomenon of mitochondrial dysfunction or a contributor to the phenotypes in mitofusin (Mfn)-depleted Drosophila melanogaster is unclear. In this paper, we show that reduction of ER dysfunction ameliorates the functional and developmental defects of flies lacking the single Mfn mitochondrial assembly regulatory factor (Marf). Ubiquitous or neuron- and muscle-specific Marf ablation was lethal, altering mitochondrial and ER morphology and triggering ER stress that was conversely absent in flies lacking the fusion protein optic atrophy 1. Expression of Mfn2 and ER stress reduction in flies lacking Marf corrected ER shape, attenuating the developmental and motor defects. Thus, ER stress is a targetable pathogenetic component of the phenotypes caused by Drosophila Mfn ablation.
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, 35129 Padua, Italy.
Valentina
V
Debattisti
Diana
D
Pendin
Elena
E
Ziviani
Andrea
A
Daga
Luca
L
Scorrano
D000818:Animals; D029721:Drosophila Proteins / Q000172:deficiency* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005816:Genetic Complementation Test; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008565:Membrane Proteins / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010654:Phenylbutyrates / Q000494:pharmacology; D034622:RNA Interference; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology
D029721:Drosophila Proteins; C527117:Marf protein, Drosophila; D008565:Membrane Proteins; D010654:Phenylbutyrates; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C075773:4-phenylbutyric acid