The antiapoptotic OPA1/Parl couple participates in mitochondrial adaptation to heat shock

Szklarz, Luiza K. Sanjuán; Scorrano, Luca

doi:10.1016/j.bbabio.2012.05.001

Cited by 27 publications

(23 citation statements)

References 53 publications

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“…) conditions. Altered mitochondrial morphology has also been observed in heat shock‐exposed cultured mouse embryonic fibroblasts (Sanjuan Szklarz & Scorrano, ). How changes in mitochondrial morphology might affect resistance of cultured muscle cells, in particular C2C12 myoblasts, to heat is largely unexplored.…”

Section: Introductionmentioning

confidence: 91%

Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Deuster

Chen

2016

The Journal of Physiology

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The regulation of mitochondrial morphology is closely coupled to cell survival during stress. We examined changes in the mitochondrial morphology of mouse C2C12 skeletal muscle cells in response to heat acclimation and heat shock exposure. Acclimated cells showed a greater survival rate during heat shock exposure than non-acclimated cells, and were characterized by long interconnected mitochondria and reduced expression of dynamin-related protein 1 (Drp1) for their mitochondrial fractions. Exposure of C2C12 muscle cells to heat shock led to apoptotic death featuring activation of caspase 3/7, release of cytochrome c and loss of cell membrane integrity. Heat shock also caused excessive mitochondrial fragmentation, loss of mitochondrial membrane potential and production of reactive oxygen species in C2C12 cells. Western blot and immunofluorescence image analysis revealed translocation of Drp1 to mitochondria from the cytosol in C2C12 cells exposed to heat shock. Mitochondrial division inhibitor 1 or Drp1 gene silencer reduced mitochondrial fragmentation and increased cell viability during exposure to heat shock. These results suggest that Drp1-dependent mitochondrial fission may regulate susceptibility to heat-induced apoptosis in muscle cells and that Drp1 may serve as a target for the prevention of heat-related injury.

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Section: Introductionmentioning

confidence: 91%

Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Deuster

Chen

2016

The Journal of Physiology

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“…Rhomboid proteases belong to a family of seven transmembrane domain serine proteases harboring serine and histidine as a catalytic dyad (1, 3), which catalyze the release of membrane-bound substrates. Rhomboid proteases (ROMs) are conserved among all kingdoms of life (1, 4) and are known to control a wide range of biologically and medically important processes ranging from insulin resistance and type 2 diabetes by the mitochondrial rhomboid protease PSARL (5), mitochondrial dysfunction and Parkinson’s disease (6, 7), mitochondrial adaptation to stress (7, 8), shedding thrombomodulin and roles in wound healing by RHBDL2 (9), and ER – associated degradation and extraction of misfolded membrane proteins by the endoplasmic reticulum resident rhomboid protease RHBDL4 (10). …”

Section: Introductionmentioning

confidence: 99%

Entamoeba histolytica rhomboid protease 1 has a role in migration and motility as validated by two independent genetic approaches

Rastew

Morf

Singh

2015

Experimental Parasitology

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Rhomboid proteins represent a recently discovered family of intramembrane proteases present in a broad range of organisms and with increasing links to human diseases. The enteric parasite Entamoeba histolytica has evolved multiple mechanisms to adapt to the human host environment and establish infection. Our recent studies identified EhROM1 as a functional E. histolytica rhomboid protease with roles in adhesion to and phagocytosis of host cells. Since those studies were performed in a non-virulent strain, roles in parasite virulence could not be assessed. We focused this study on the comparison and validation of two genetic manipulation techniques: overexpression of a dominant-negative catalytic mutant of EhROM1 and knock down of EhROM1 using a RNAi-based silencing approach followed by functional studies of phenotypic analyses in virulent parasites. Both the EhROM1 catalytic mutant and parasites with EhROM1 downregulation were reduced in cytotoxicity, hemolytic activity, and directional and non-directional transwell migration. Importantly, the role for EhROM1 in cell migration mimics similar roles for rhomboid proteases from mammalian and apicomplexan systems. However, the EhROM1 catalytic mutant and EhROM1 downregulation parasites had different phenotypes for erythrophagocytosis, while complement resistance was not affected in either strain. In summary, in this study we genetically manipulated E. histolytica rhomboid protease EhROM1 by two different approaches and identified similarly attenuated phenotypes by both approaches, suggesting a novel role for EhROM1 in amebic motility.

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“…PARL can interact with OPA1 during apoptosis by regulating apoptotic cristae remodeling and cytochrome c release20. Moreover, PARL together with OPA1 can control mitochondrial morphology19 and participate in mitochondrial adaptation to heat shock21. Genetic variants in the PARL gene can influence mitochondrial content22 and susceptibility to Parkinson’s disease23, type 2 diabetes24 and LHON25, although there were some negative reports2627.…”

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confidence: 99%

Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China

Wang

Feng

et al. 2016

Sci Rep

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Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy.

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The antiapoptotic OPA1/Parl couple participates in mitochondrial adaptation to heat shock

Cited by 27 publications

References 53 publications

Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Role of dynamin‐related protein 1‐mediated mitochondrial fission in resistance of mouse C2C12 myoblasts to heat injury

Entamoeba histolytica rhomboid protease 1 has a role in migration and motility as validated by two independent genetic approaches

Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China

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