Details

Autor(en) / Beteiligte

• Graham, Brett H.
• Li, Zhihong
• Alesii, Erminio P.
• Versteken, Patrik
• Lee, Cynthia
• Wang, Jennifer
• Craigen, William J.

Titel

Neurologic Dysfunction and Male Infertility in Drosophila porin Mutants

Ist Teil von

• The Journal of biological chemistry, 2010-04, Vol.285 (15), p.11143-11153

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2010

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Voltage-dependent anion channels (VDACs) are a family of small pore-forming proteins of the mitochondrial outer membrane found in all eukaryotes. VDACs play an important role in the regulated flux of metabolites between the cytosolic and mitochondrial compartments, and three distinct mammalian isoforms have been identified. Animal and cell culture experiments suggest that the various isoforms act in disparate roles such as apoptosis, synaptic plasticity, learning, muscle bioenergetics, and reproduction. In Drosophila melanogaster, porin is the ubiquitously expressed VDAC isoform. Through imprecise excision of a P element insertion in the porin locus, a series of hypomorphic alleles have been isolated, and analyses of flies homozygous for these mutant alleles reveal phenotypes remarkably reminiscent of mouse VDAC mutants. These include partial lethality, defects of mitochondrial respiration, abnormal muscle mitochondrial morphology, synaptic dysfunction, and male infertility, which are features often observed in human mitochondrial disorders. Furthermore, the observed synaptic dysfunction at the neuromuscular junction in porin mutants is associated with a paucity of mitochondria in presynaptic termini. The similarity of VDAC mutant phenotypes in the fly and mouse clearly indicate a fundamental conservation of VDAC function. The establishment and validation of a new in vivo model for VDAC function in Drosophila should provide a valuable tool for further genetic dissection of VDAC role(s) in mitochondrial biology and disease, and as a model of mitochondrial disorders potentially amenable to the development of treatment strategies.