Oxidative pentose phosphate pathway and glucose anaplerosis support maintenance of mitochondrial <scp>NADPH</scp> pool under mitochondrial oxidative stress

Moon, Sun Jin; Dong, Wentao; Stephanopoulos, Gregory; Sikes, Hadley D.

doi:10.1002/btm2.10184

Cited by 49 publications

(40 citation statements)

References 75 publications

(185 reference statements)

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“…CCl 4 is a commonly used toxin to cause liver injury since it can induce free radicals and trigger peroxide chain reaction, leading to lipid peroxidation in phospholipid‐rich and membrane structures. Mitochondria contain phospholipid bilayers, and especially the inner membrane is the main site of cellular energy production (OXPHOS) 5 . The free radicals damage the capability of OXPHOS and decrease ATP production.…”

Section: Discussionmentioning

confidence: 99%

“…The primary mechanism of CCl 4 ‐induced liver injury is to induce free radical production and damage hepatic mitochondrial function, which represents both reduced mitochondrial mass and impaired metabolism of the remaining mitochondria 4 . Therefore, the protection of mitochondrial function and prevention of the impairment caused by free radicals have become potential therapeutic approaches in rescuing cell function 5,6 …”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

Zhao

Hou

Zhou

et al. 2020

Bioengineering & Transla Med

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Carbon tetrachloride (CCl4)‐induced liver injury is predominantly caused by free radicals, in which mitochondrial function of hepatocytes is impaired, accompanying with the production of ROS and decreased ATP energy supply in animals intoxicated with CCl4. Here we explored a novel therapeutic approach, mitochondrial transplantation therapy, for treating the liver injury. The results showed that mitochondria entered hepatocytes through macropinocytosis pathway, and thereby cell viability was recovered in a concentration‐dependent manner. Mitochondrial therapy could increase ATP supply and reduce free radical damage. In liver injury model of mice, mitochondrial therapy significantly improved liver function and prevented tissue fibrogenesis. Transcriptomic data revealed that mitochondrial unfold protein response (UPRmt), a protective transcriptional response of mitochondria‐to‐nuclear retrograde signaling, would be triggered after mitochondrial administration. Then the anti‐oxidant genes were up‐regulated to scavenge free radicals. The mitochondrial function was rehabilitated through the transcriptional activation of respiratory chain enzyme and mitophage‐associated genes. The protective response re‐balanced the cellular homeostasis, and eventually enhanced stress resistance that is linked to cell survival. The efficacy of mitochondrial transplantation therapy in the animals would suggest a novel approach for treating liver injury caused by toxins.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

Zhao

Hou

Zhou

et al. 2020

Bioengineering & Transla Med

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“…The pentose phosphate pathway is critical to the production of ribobased products (such as DNA, RNA), precursors of aromatic amino acid biosynthesis pathways, and reduction equivalents (such as NADPH) needed to maintain redox equilibrium and lipid synthesis. In addition, it also plays an important role in cell resistance to oxidative stress (Moon et al, 2020;Xu et al, 2017). Therefore, the activity of transketolase is related to the F I G U R E 4 Analysis of differentially expressed genes in amino acid biosynthesis pathway of different strains at different temperatures.…”

Section: Mining Key Genes Of Thiamine Pathwaymentioning

confidence: 99%

Conferring thermotolerant phenotype to wild‐type Yarrowia lipolytica improves cell growth and erythritol production

Qiu

et al. 2021

Biotech & Bioengineering

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In microbial engineering, heat stress is an important environmental factor modulating cell growth, metabolic flux distribution and the synthesis of target products.Yarrowia lipolytica, as a GARS (generally recognized as safe) nonconventional yeast, has been widely used in the food industry, especially as the host of erythritol production. Biomanufacturing economics is limited by the high operational cost of cooling energy in large-scale fermentation. It is of great significance to select thermotolerant Y. lipolytica to reduce the cooling cost and elucidate the heatresistant mechanism at molecular level. For this purpose, we performed adaptive evolution and obtained a thermotolerant strain named Y. lipolytica BBE-18. Transcriptome analysis allows us to identify four genes in thiamine metabolism pathway that are responsible for the complicated thermotolerant phenotype. The heatresistant phenotype was validated with the model strain Y. lipolytica Po1f by overexpression of single and combined genes. Then, conferring the thermotolerant phenotype to the wild-type Y. lipolytica BBE-17 enable the strain to produce threetimes more erythritol of the control strain with 3°C higher than optimal cultivation temperature. To our knowledge, this is the first report on engineering heat-resistant phenotype to improve the erythritol production in Y. lipolytica. However, due to the increase of culture temperature, a large amount of adenosine triphosphate is consumed to ensure the life activities of Y. lipolytica which limits the potential of cell synthetic products to a certain extent. Even so, this study provides a reference for Y. lipolytica to produce other products under high temperature.

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“…In contrast, chemical probes for NAD(P)H are able to penetrate the mitochondria in human cells 162 and the NADPH biosensor iNap has been successfully expressed in the mitochondria of human cells. 163 Improvements could be made with greater diversity of cellular targeting of chemical probes and biosensors, e.g. Apollo-NADP + for NADP + or LigA-cpVenus for NAD + detection.…”

Section: Fluorescent Protein Sensorsmentioning

confidence: 99%

Measuring ROS and redox markers in plant cells

et al. 2021

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Oxidative pentose phosphate pathway and glucose anaplerosis support maintenance of mitochondrial NADPH pool under mitochondrial oxidative stress

Cited by 49 publications

References 75 publications

Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

Mitochondrial transplantation therapy inhibit carbon tetrachloride‐induced liver injury through scavenging free radicals and protecting hepatocytes

Conferring thermotolerant phenotype to wild‐type Yarrowia lipolytica improves cell growth and erythritol production

Measuring ROS and redox markers in plant cells

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