Mitochondrial Voltage-Dependent Anion Channel Protein Por1 Positively Regulates the Nuclear Localization of Saccharomyces cerevisiae AMP-Activated Protein Kinase

Shevade, Aishwarya; Strogolova, Vera; Orlova, Marianna; Yeo, Chay Teng; Kuchin, Sergei

doi:10.1128/msphere.00482-17

Cited by 10 publications

(12 citation statements)

References 48 publications

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“…5D). These results are consistent with a growing number of papers that have shown that a sub-population of the Snf1-Gal3 isoform is present in the nucleus under normal conditions 52 60 70 , as well as enriched in the nucleus upon glucose starvation 34 35 36 . In addition, Sak1 is needed for Snf1 nuclear localization 71 .…”

Section: Discussionsupporting

confidence: 92%

“…Further studies need to be executed to address if Sip1 or Sip2 can translocate into the nucleus in the absence of Gal83. Intriguingly, just recently the Mitochondrial Voltage-Dependent Anion Channel Protein Por1 (yVDAC1) has been shown to enhance Snf1 nuclear enrichment by promoting the nuclear enrichment of Gal83 70 . This unexpected finding serves to emphasize that there is still much to learn about the role Snf1 kinase plays in response to changing environmental conditions.…”

Section: Discussionmentioning

confidence: 99%

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Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

et al. 2018

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Eukaryotic cells, when faced with unfavorable environmental conditions, mount either pro-survival or pro-death programs. The conserved cyclin C-Cdk8 kinase plays a key role in this decision. Both are members of the Cdk8 kinase module that, along with Med12 and Med13, associate with the core Mediator complex of RNA polymerase II. In Saccharomyces cerevisiae, oxidative stress triggers Med13 destruction, which releases cyclin C into the cytoplasm to promote mitochondrial fission and programmed cell death. The SCFGrr1 ubiquitin ligase mediates Med13 degradation dependent on the cell wall integrity pathway, MAPK Slt2. Here we show that the AMP kinase Snf1 activates a second SCFGrr1 responsive degron in Med13. Deletion of Snf1 resulted in nuclear retention of cyclin C and failure to induce mitochondrial fragmentation. This degron was able to confer oxidative-stress-induced destruction when fused to a heterologous protein in a Snf1 dependent manner. Although snf1∆ mutants failed to destroy Med13, deleting the degron did not prevent destruction. These results indicate that the control of Med13 degradation following H2O2 stress is complex, being controlled simultaneously by CWI and MAPK pathways.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

et al. 2018

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“…In S. cerevisiae, Gal83 phosphorylation sites have been identified in high-throughput studies [95], but the effect of such modifications is not known. Some evidence suggests a role for the mitochondrial voltage-dependent anion channel (VDAC) protein, Por1, promoting Gal83 nuclear localization by a mechanism that is distinct from Snf1 activation during growth in glycerol/ethanol [96], and for the nuclear export receptor, Crm1, in the nuclear exclusion of Gal83 during growth on abundant glucose [97]. P. pastoris OXPHOS mutants share phenotypes of DScpor1 mutant, such as normal Snf1 activation by glucose derepression and the absence of induction of genes regulated by SNF1 signaling [96].…”

Section: Feedback Loop Between Peroxisomes and Mitochondria Senses Cellular Metabolic Statusmentioning

confidence: 99%

“…Some evidence suggests a role for the mitochondrial voltage-dependent anion channel (VDAC) protein, Por1, promoting Gal83 nuclear localization by a mechanism that is distinct from Snf1 activation during growth in glycerol/ethanol [96], and for the nuclear export receptor, Crm1, in the nuclear exclusion of Gal83 during growth on abundant glucose [97]. P. pastoris OXPHOS mutants share phenotypes of DScpor1 mutant, such as normal Snf1 activation by glucose derepression and the absence of induction of genes regulated by SNF1 signaling [96]. However, the deletion of the only POR1 homolog, or overexpression of Por1 in P. pastoris, did not produce the same phenotypes observed in the OXPHOS mutants and Gal83 localization was unaffected by Por1.…”

Section: Feedback Loop Between Peroxisomes and Mitochondria Senses Cellular Metabolic Statusmentioning

confidence: 99%

OXPHOS deficiencies affect peroxisome proliferation by downregulating genes controlled by the SNF1 signaling pathway

Farré

Carolino

Devanneaux

et al. 2021

Preprint

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How environmental cues influence peroxisome proliferation, particularly through other organelles, remains largely unknown. Yeast peroxisomes metabolize all fatty acids (FA), and methylotrophic yeasts also metabolize methanol. NADH and acetyl-CoA, the products of these pathways enter mitochondria for ATP production, and for anabolic reactions. During the metabolism of FA and/or methanol, the mitochondrial oxidative phosphorylation (OXPHOS) pathway accepts NADH for ATP production and maintains cellular redox balance. Remarkably, peroxisome proliferation in Pichia pastoris was abolished in NADH shuttling and OXPHOS mutants affecting complex I or III, or by the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), indicating ATP depletion causes the phenotype. We show that mitochondrial OXPHOS deficiency inhibits the expression of several peroxisomal proteins implicated in FA and methanol metabolism, as well as in peroxisome division and proliferation. These genes are regulated by the Snf1 complex (SNF1), a pathway generally activated by high AMP and low ATP. Consistent with this mechanism, in OXPHOS mutants, Snf1 is activated by phosphorylation, but Gal83, its interacting subunit, fails to translocate to the nucleus. Phenotypic defects in peroxisome proliferation observed in the OXPHOS mutants, and phenocopied by the Δgal83 mutant, were rescued by deletion of three transcriptional repressor genes (MIG1, MIG2 and NRG1) controlled by SNF1 signaling. We uncovered here the mechanism by which peroxisomal and mitochondrial metabolites influence redox and energy metabolism, while also influencing peroxisome biogenesis and proliferation, thereby exemplifying interorganellar communication and interplay involving peroxisomes, mitochondria, cytosol and the nucleus. We discuss the physiological relevance of this work in view of human OXPHOS deficiencies.

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“…Recently, AMPK-related protein kinase-5 (ARK5), a crucial member of the human AMP-activated protein kinases (AMPKs) family, has been identified to be associated with metastasis of cancer cells (4). Metastasis is a complex multistep process involving cell migration and invasion.…”

Section: Introductionmentioning

confidence: 99%

Knockdown of ARK5 expression suppresses invasion of ovarian cancer cells

Wang

Li³

et al. 2019

Mol Med Report

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The aim of the current study was to investigate the effects and the molecular mechanisms of ARK5 in ovarian cancer cell invasion. The plasmid pGCsilencerU6/GFP/Neo-RNAi-ARK5 and the control vector with a scramble sequence were transfected into SKOV3 cells to establish ARK5-deficient SKOV3 cells (siARK5/SKOV3) and a control cell line (Scr/SKOV3), respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were used to determine the mRNA and protein expression levels of ARK5. Migration and invasion abilities of SKOV3 cells were determined in chemotaxis and invasion assays, respectively. The epidermal growth factor-1 (EGF-1)-induced expression of matrix metallopeptidase (MMP)-2 and MMP-9, epithelial-mesenchymal transition (EMT) and phosphorylation of mechanistic target of rapamycin kinase (mTOR) in siARK5/SKOV3 and Scr/SKOV3 cells were detected by western blot. RT-PCR and western blot analyses demonstrated that the expression of ARK5 was significantly downregulated in siARK5/SKOV3 cells at the mRNA and protein levels (P<0.01). The migration and invasion abilities of siARK5/SKOV3 cells were markedly decreased compared with Scr/SKOV3 cells (P<0.01). In addition, the results demonstrated that EGF-1-induced expression of MMP-2 and MMP-9, EMT and phosphorylation of mTOR were suppressed in siARK5/SKOV3 cells as compared with Scr/SKOV3 cells (P<0.01). The current study demonstrated that ARK5 is a critical factor involved in SKOV3 cell invasion and ARK5 increases invasive potential by promoting EMT and activating the Akt-mTOR-MMPs pathway.

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Mitochondrial Voltage-Dependent Anion Channel Protein Por1 Positively Regulates the Nuclear Localization of Saccharomyces cerevisiae AMP-Activated Protein Kinase

Cited by 10 publications

References 48 publications

Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

Snf1 cooperates with the CWI MAPK pathway to mediate the degradation of Med13 following oxidative stress

OXPHOS deficiencies affect peroxisome proliferation by downregulating genes controlled by the SNF1 signaling pathway

Knockdown of ARK5 expression suppresses invasion of ovarian cancer cells

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