Abstract
Voltage-dependent anion channel (VDAC) has been suggested to be a mediator of mitochondrial-dependent cell death induced by Ca2+ overload, oxidative stress and Bax-Bid activation. To confirm this hypothesis in vivo, we generated and characterized Drosophila VDAC (porin) mutants and found that Porin is not required for mitochondrial apoptosis, which is consistent with the previous mouse studies. We also reported a novel physiological role of Porin. Loss of porin resulted in locomotive defects and male sterility. Intriguingly, porin mutants exhibited elongated mitochondria in indirect flight muscle, whereas Porin overexpression produced fragmented mitochondria. Through genetic analysis with the components of mitochondrial fission and fusion, we found that the elongated mitochondria phenotype in porin mutants were suppressed by increased mitochondrial fission, but enhanced by increased mitochondrial fusion. Furthermore, increased mitochondrial fission by Drp1 expression suppressed the flight defects in the porin mutants. Collectively, our study showed that loss of Drosophila Porin results in mitochondrial morphological defects and suggested that the defective mitochondrial function by Porin deficiency affects the mitochondrial remodeling process.
Highlights
Mitochondria undergo mitochondrial membrane permeability transition (MPT) after opening of a channel called mitochondrial permeability transition pore (PTP) when cells succumb to apoptosis [1]
Researchers studying the function of PTP components have questioned about the interaction between mitochondrial fusion and fission and the MPT components [18]
We generated Voltage-dependent anion channel (VDAC), one of the core components of PTP, null flies, but found that Porin is dispensable for oxidative stress, Ca2+ overload- or Bax activation-induced cell death (Figure 3)
Summary
Mitochondria undergo mitochondrial membrane permeability transition (MPT) after opening of a channel called mitochondrial permeability transition pore (PTP) when cells succumb to apoptosis [1]. PTP is a site for cytochrome c release, which leads to caspase activation and cell death. PTP is minimally composed of three proteins, VDAC (in the outer membrane), the adenine nucleotide translocase (ANT, in the inner membrane) and cyclophilin D (CypD, in the matrix). These PTP components have been initially proposed to be critically involved in mitochondrial cell death induced by Ca2+ overload, oxidative stress and Bax-Bid activation. Recent studies have demonstrated that VDAC and ANT are not essential for MPT in cell death but only cyclophilin D required [2,3,4]. The physiological role of VDAC and ANT remains questionable
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
