Drosophila Porin/VDAC Affects Mitochondrial Morphology

Park, Jeehye; Kim, Yongsung; Choi, Sekyu; Koh, Hyongjong; Lee, Sangeun; Kim, Jin Man; Chung, Jongkyeong

doi:10.1371/journal.pone.0013151

Cited by 53 publications

(45 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). These modifications of mitochondrial morphology in Arabidopsis are similar to the ones described in muscles of mouse (Anflous et al 2001;Sampson et al 2001) and in drosophila (Graham et al 2010;Park et al 2010). They are often associated with cell death, in particular during necrosis in plants (van Doorn et al 2011), and could explain the presence of yellow spots and the high production of ROS in atvdac1 and atvdac4 leaves (Fig.…”

Section: Absence Of Atvdac1 Atvdac2 and Atvdac4 Proteins Results In supporting

confidence: 76%

Voltage-dependent-anion-channels (VDACs) in Arabidopsis have a dual localization in the cell but show a distinct role in mitochondria

et al. 2012

View full text Add to dashboard Cite

In mammals, the Voltage-dependent anion channels (VDACs) are predominant proteins of the outer mitochondrial membrane (OMM) where they contribute to the exchange of small metabolites essential for respiration. They were shown to be as well associated with the plasma membrane (PM) and act as redox enzyme or are involved in ATP release for example. In Arabidopsis, we show that four out of six genomic sequences encode AtVDAC proteins. All four AtVDACs are ubiquitously expressed in the plant but each of them displays a specific expression pattern in root cell types. Using two complementary approaches, we demonstrate conclusively that the four expressed AtVDACs are targeted to both mitochondria and plasma membrane but in differential abundance, AtVDAC3 being the most abundant in PM, and conversely, AtVDAC4 almost exclusively associated with mitochondria. These are the first plant proteins to be shown to reside in both these two membranes. To investigate a putative function of AtVDACs, we analyzed T-DNA insertion lines in each of the corresponding genes. Knock-out mutants for AtVDAC1, AtVDAC2 and AtVDAC4 present slow growth, reduced fertility and yellow spots in leaves when atvdac3 does not show any visible difference compared to wildtype plants. Analyses of atvdac1 and atvdac4 reveal that yellow areas correspond to necrosis and the mitochondria are swollen in these two mutants. All these results suggest that, in spite of a localization in plasma membrane for three of them, AtVDAC1, AtVDAC2 and AtVDAC4 have a main function in mitochondria.

show abstract

Section: Absence Of Atvdac1 Atvdac2 and Atvdac4 Proteins Results In supporting

confidence: 76%

Voltage-dependent-anion-channels (VDACs) in Arabidopsis have a dual localization in the cell but show a distinct role in mitochondria

et al. 2012

View full text Add to dashboard Cite

show abstract

“…As summarized by [73], VDAC interactions with different proteins contribute to apoptosis, cytoskeleton functions, Ca 2+ and oxidative-redox homeostasis as well as energy transformation (Figure 2). There are also data pointing at interaction between VDAC and mitochondrial trafficking and fusion/ fission machinery [74,75]. Consequently, VDAC modulation may affect processes that are known to be affected by VDAC directly; i.e., the respiratory chain, transcriptional regulation and protein import, Ca 2+ balance, oxidative stress and apoptosis, or might be affected due to interaction between VDAC and the involved proteins.…”

Section: Vdac As a Versatile Proteinmentioning

confidence: 99%

VDAC as a Potential Target in Huntingtons Disease Therapy: The State of the Art

Karachitos¹,

Grobys²

2015

Pharmaceut Reg Affairs

View full text Add to dashboard Cite

It is becoming increasingly evident that mitochondria dysfunction plays an important role in pathogenesis of Huntington's disease (HD). However, the underlying mechanism is still needs to be explained. The crucial aspect of the explanation is to indicate the upstream events in mitochondria dysfunction that could contribute to HD. In the review we propose the defect of voltage-dependent anion-selective channel (VDAC), as a causative event in HDrelated mitochondria dysfunction. Thus, we propose to consider VDAC as a crucial element in HD etiology and consequently as a reasonable target for therapeutic interventions in HD, based on developing novel therapeutic strategies eliminating mitochondria dysfunction.Keywords: Huntington's disease; VDAC; Mitochondria; Therapy Huntington's DiseaseHuntington's disease (HD) is a progressive and fatal neurodegenerative disease with a prevalence of about 5-10/100 000. Clinically, the disease is characterized by progressive chorea (involuntary dance-like movements), rigidity, weight loss, dementia, seizures and psychiatric disturbances such as depression, withdrawal and irritability. These symptoms including cognitive deterioration, psychiatric disturbances, and movement disorders result from a selective and continuous loss of neurons from the striatum and deep layers of the cerebral cortex although other brain regions such as thalamus and subthalamic nucleus are also affected [1][2][3]. Current treatments for HD relieve merely the symptoms and address the control of behavioral symptoms, motor sedatives, cognitive enhancers, and neuroprotective agents [4,5] but are not able to restore neuronal function nor to stop the insidious loss of neurons. As summarized by Kumar et al. [6], although there is an intensive research concerning development of neuroprotective strategies such as fetal neural transplantation, RNA interference (RNAi) and transglutaminase inhibitors (TGaseI), effective therapeutic strategies may not be developed until the next few decades. Thus, a new therapeutic approach involving new potential targets and to start before the symptomatic stage could contribute to HD treatment to be more specific and effective. This, in turn, requires further studies concerning molecular mechanisms underlying HD.The genetic hallmark of HD is an expansion of an unstable trinucleotide CAG repeat region within the first exon of the gene encoding the protein Huntington (Htt). This results in synthesis of its mutant form (mHtt) containing more than 36 glutamine residues at N terminus although the possible contribution of mHtt encoding mRNA, i.e. toxic mRNA in HD etiology has also been suggested [7]. HD inheritance is autosomal dominant and consequently the prevailing view is that mHtt mediated symptoms result from a toxic gain-offunction mechanism although loss-of-function mechanisms for mHtt and Htt are also proposed [8,9]. Htt is conserved among vertebrates [10], is localized mainly in cytoplasm and exhibits anti-apopptotic properties [11,12]. Importantly, Htt expression in diffe...

show abstract

“…Numerous experiments have been conducted examining localization, identification, and expression of VDACs in spermatozoa (8,9,(22)(23)(24)(25)(26)(27)(28), and Liu et al (26,28) reported that VDAC expression was related to sperm motility. Nevertheless, the roles of VDACs in spermatozoa during reproduction are not yet fully understood.…”

mentioning

confidence: 99%