Overexpression of the peroxin Pex34p suppresses impaired acetate utilization in yeast lacking the mitochondrial aspartate/glutamate carrier Agc1p

Chalermwat, Chalongchai; Thosapornvichai, Thitipa; Wongkittichote, Parith; Phillips, John D.; Cox, James E.; Jensen, Amornrat Naranuntarat; Wattanasirichaigoon, Duangrurdee; Jensen, Laran T.

doi:10.1093/femsyr/foz078

Cited by 4 publications

(5 citation statements)

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“…Enhanced chronological lifespan can also be mediated by the activation of mitochondrial retrograde and oxidative stress responses to overcome mitochondrial stresses [38,39]. We have previously shown that PEX34 over-expression induced mitochondrial retrograde signaling in acetate medium [37], suggesting that PEX34 over-expression can induce these stress responses resulting in increased longevity in yeasts.…”

Section: Discussionmentioning

confidence: 99%

“…Gpd1p is required for glycerol production, which can protect cells under several stress conditions, such as osmotic stress, oxidative stress, or ER stress [35,36]. Our group has previously shown that PEX34 over-expression results in aberrant ER morphology and induces ER stress in an acetate medium [37]. It is possible that PEX34 over-expression also induces ER stress in the stationary phase of glucose-grown cells, resulting in the induction of GPD1-mediated NAD + regeneration in peroxisomes.…”

Section: Discussionmentioning

confidence: 99%

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Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency

et al. 2020

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Citrin is a liver-specific mitochondrial aspartate–glutamate carrier encoded by SLC25A13. Citrin deficiency caused by SLC25A13 mutation results in carbohydrate toxicity, citrullinemia type II, and fatty liver diseases, the mechanisms of some of which remain unknown. Citrin shows a functional homolog in yeast aspartate-glutamate carrier (Agc1p) and agc1Δ yeasts are used as a model organism of citrin deficiency. Here, we found that agc1Δ yeasts decreased fat utilization, impaired NADH balance in peroxisomes, and decreased chronological lifespan. The activation of GPD1-mediated NAD+ regeneration in peroxisomes by GPD1 over-expression or activation of the malate–oxaloacetate NADH peroxisomal shuttle, by increasing flux in this NADH shuttle and over-expression of MDH3, resulted in lifespan extension of agc1Δ yeasts. In addition, over-expression of PEX34 restored longevity of agc1Δ yeasts as well as wild-type cells. The effect of PEX34-mediated longevity required the presence of the GPD1-mediated NADH peroxisomal shuttle, which was independent of the presence of the peroxisomal malate–oxaloacetate NADH shuttle and PEX34-induced peroxisome proliferation. These data confirm that impaired NAD+ regeneration in peroxisomes is a key defect in the yeast model of citrin deficiency, and enhancing peroxisome function or inducing NAD+ regeneration in peroxisomes is suggested for further study in patients’ hepatocytes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency

et al. 2020

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“…Another illustration is the mammalian MCS between lysosomes, POs, and the ER, involved in cholesterol transport between the lysosomes and the ER, via the POs ( Chu et al, 2021 ; Xiao et al, 2019 ). Citrate is transferred from POs to mitochondria through expanded contact sites following PEX34 overexpression in yeast ( Chalermwat et al, 2019 ). Very long chain fatty acids (VLCFA) are transported by the MCS involving VAPB and ACBD4/5 ( Costello et al, 2017 ).…”

Section: Regulation Of Peroxisomal And/or Mitochondrial Divisionmentioning

confidence: 99%

Convergent and divergent mechanisms of peroxisomal and mitochondrial division

Subramani,

Shukla,

Farre

2023

Journal of Cell Biology

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Organelle division and segregation are important in cellular homeostasis. Peroxisomes (POs) and mitochondria share a core division machinery and mechanism of membrane scission. The division of each organelle is interdependent not only on the other but also on other organelles, reflecting the dynamic communication between subcellular compartments, even as they coordinate the exchange of metabolites and signals. We highlight common and unique mechanisms involved in the fission of these organelles under the premise that much can be gleaned regarding the division of one organelle based on information available for the other.

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“…Yeast transformations were performed using the lithium acetate procedure [81] and transformants were selected using synthetic complete (SC) medium lacking uracil. Promoter-lacZ reporter plasmids pLJ519 (ACT1-lacZ) and pLJ440 (FET3-lacZ) have been previously described [82,83].…”

Section: Yeast Strains Culture Conditions and Plasmidsmentioning

confidence: 99%

Disruption in iron homeostasis and impaired activity of iron-sulfur cluster containing proteins in the yeast model of Shwachman-Diamond syndrome

et al. 2020

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Background Shwachman-Diamond syndrome (SDS) is a congenital disease that affects the bone marrow, skeletal system, and pancreas. The majority of patients with SDS have mutations in the SBDS gene, involved in ribosome biogenesis as well as other processes. A Saccharomyces cerevisiae model of SDS, lacking Sdo1p the yeast orthologue of SBDS, was utilized to better understand the molecular pathogenesis in the development of this disease. Results Deletion of SDO1 resulted in a three-fold over-accumulation of intracellular iron. Phenotypes associated with impaired iron-sulfur (ISC) assembly, up-regulation of the high affinity iron uptake pathway, and reduced activities of ISC containing enzymes aconitase and succinate dehydrogenase, were observed in sdo1∆ yeast. In cells lacking Sdo1p, elevated levels of reactive oxygen species (ROS) and protein oxidation were reduced with iron chelation, using a cell impermeable iron chelator. In addition, the low activity of manganese superoxide dismutase (Sod2p) seen in sdo1∆ cells was improved with iron chelation, consistent with the presence of reactive iron from the ISC assembly pathway. In yeast lacking Sdo1p, the mitochondrial voltage-dependent anion channel (VDAC) Por1p is over-expressed and its deletion limits iron accumulation and increases activity of aconitase and succinate dehydrogenase. Conclusions We propose that oxidative stress from POR1 over-expression, resulting in impaired activity of ISC containing proteins and disruptions in iron homeostasis, may play a role in disease pathogenesis in SDS patients.

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Overexpression of the peroxin Pex34p suppresses impaired acetate utilization in yeast lacking the mitochondrial aspartate/glutamate carrier Agc1p

Cited by 4 publications

References 81 publications

Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency

Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency

Convergent and divergent mechanisms of peroxisomal and mitochondrial division

Disruption in iron homeostasis and impaired activity of iron-sulfur cluster containing proteins in the yeast model of Shwachman-Diamond syndrome

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