Output Regulation and Function Optimization of Mitochondria in Eukaryotes

Zeng, Miaolin; Du, Haixia; Yang, Jiehong; Wan, Haitong

doi:10.3389/fcell.2020.598112

Cited by 7 publications

(3 citation statements)

References 135 publications

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“…Electron donors feed into the electron transport chain, which moves protons across the inner mitochondrial membrane to produce a gradient capable of driving energy output (adenosine triphosphate: ATP). This process produces reactive oxygen species (ROS) as a byproduct 189 . A) bLR-like animals have a pattern of upregulated expression suggesting elevated oxidative phosphorylation, but potentially also reduced sensitivity to cellular need in a manner leading to excessive ROS production and neuroimmune activation under conditions of elevated activity such as stress.…”

Section: Resultsmentioning

confidence: 99%

“…During this process, glucose metabolites are fed into the Tricarboxylic Acid Cycle (TCA or Krebs Cycle) within the mitochondrial matrix. The TCA cycle generates electron donors for an electron transport chain, which increases the proton gradient across the inner mitochondrial membrane driving energy production (including production of adenosine triphosphate or ATP; (Zeng et al, 2020)).…”

Section: Bioenergetics and Oxidative Phosphorylationmentioning

confidence: 99%

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Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F₂Cross of Selectively-Bred Rats

Hebda-Bauer

Hagenauer

Blandino

et al. 2022

Preprint

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In humans, differences in temperament are highly predictive of classes of psychopathology classified as externalizing versus internalizing disorders. To better understand the genetic and neural causes of temperamental differences, we have selectively bred two lines of rats based on their exploration of a novel environment. The bred High Responder (bHR) and bred Low Responder (bLR) rats show contrasting heritable behaviors that map onto human temperamental differences and are associated with two paths to drug abuse—sensation seeking and reactivity to psychosocial stress. To elucidate the genes that underlie the divergent behavior of bHR/bLR rats, we created a bHRxbLR F0-F1-F2 cross and performed behavioral testing, transcriptional profiling, and genetic sequencing. We used RNA-Seq to characterize hippocampal tissue in F0s (n=24, n=6 per phenotype /sex) and F2s (n=250, n=125 per sex) to identify differentially expressed genes related to bHR/bLR lineage and phenotypical behaviors: locomotor response to novelty, anxiety, and Pavlovian Conditioned Approach (PavCA).We found that bHR/bLR phenotypical behaviors remained correlated in the F2s, implying a shared genetic basis. We also found robust differences in hippocampal transcriptional profiles associated with bHR/bLR lineage in the F0s which surpassed the differences associated with sex. These distinct expression profiles were predictive of gene expression patterns associated with F2 bHR/bLR behavior. We then prioritized bHR/bLR differentially expressed genes identified in our current and previous studies as candidates for mediating bHR/bLR phenotypical behaviors in F2s. Seventeen genes were differentially expressed in association with locomotor response to novelty, many of which also had nominal relationships with PavCA behavior. Seven of these genes were located near (+/−1MB) quantitative trait loci for bHR/bLR phenotypical behavior identified in our previous exome sequencing or genome wide association studies: AABR07071904, Ucp2, Ttc30a1, Fzd6, Spg7, Vps9d1, and Afg3l1. We also identified convergence between our model and other genetic rat models targeting internalizing behaviors, with 26 hippocampal genes showing shared patterns of differential expression, including Tmem144 and Mfge8. Our findings provide strong candidates for elucidating genetic and neurobiological factors that may shape differences in temperament and modulate vulnerability to psychiatric and addictive disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Bioenergetics and Oxidative Phosphorylationmentioning

confidence: 99%

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F₂Cross of Selectively-Bred Rats

Hebda-Bauer

Hagenauer

Blandino

et al. 2022

Preprint

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show abstract

“…It is almost entirely oxidized to carbon dioxide and water with concurrent production of ATP to meet the cellular energy demand. Glucose figures in various metabolic pathways of the brain, including glycolysis, the pentose phosphate pathway, and (in astrocytes only) glycogenesis [ 107 , 108 ]. Following AIS, neurons depend highly on an uninterrupted ATP supply from glycolysis [ 109 ].…”

Section: Tfeb Regulates Pathophysiological Processes In Ischemic Strokementioning

confidence: 99%

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke

Shao

Lang

Ding

et al. 2024

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Transcription factor EB (TFEB) is an important endogenous defensive protein that responds to ischemic stimuli. Acute ischemic stroke is a growing concern due to its high morbidity and mortality. Most survivors suffer from disabilities such as numbness or weakness in an arm or leg, facial droop, difficulty speaking or understanding speech, confusion, impaired balance or coordination, or loss of vision. Although TFEB plays a neuroprotective role, its potential effect on ischemic stroke remains unclear. This article describes the basic structure, regulation of transcriptional activity, and biological roles of TFEB relevant to ischemic stroke. Additionally, we explore the effects of TFEB on the various pathological processes underlying ischemic stroke and current therapeutic approaches. The information compiled here may inform clinical and basic studies on TFEB, which may be an effective therapeutic drug target for ischemic stroke.

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Mitochondrial tRNA^Glu 14693A > G Mutation, an “Enhancer” to the Phenotypic Expression of Leber's Hereditary Optic Neuropathy

Jin,

Gan,

et al. 2024

Advanced Science

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Leber's hereditary optic neuropathy (LHON), a maternally inherited ocular disease, is predominantly caused by mitochondrial DNA (mtDNA) mutations. Mitochondrial tRNA variants are hypothesized to amplify the pathogenic impact of three primary mutations. However, the exact mechanisms remained unclear. In the present study, the synergistic effect of the tRNAGlu 14693A > G and ND6 14484T > C mutations in three Chinese families affected by LHON is investigated. The m.14693A > G mutation nearly abolishes the pseudouridinylation at position 55 of tRNAGlu, leading to structural abnormalities, decreased stability, aberrant mitochondrial protein synthesis, and increased autophagy. In contrast, the ND6 14484T > C mutation predominantly impairs complex I function, resulting in heightened apoptosis and virtually no induction of mitochondrial autophagy compared to control cell lines. The presence of dual mutations in the same cell lines exhibited a coexistence of both upregulated cellular stress responses to mitochondrial damage, indicating a scenario of autophagy and mutation dysregulation within these dual‐mutant cell lines. The data proposes a novel hypothesis that mitochondrial tRNA gene mutations generally lead to increased mitochondrial autophagy, while mutations in genes encoding mitochondrial proteins typically induce apoptosis, shedding light on the intricate interplay between different genetic factors in the manifestation of LHON.

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Output Regulation and Function Optimization of Mitochondria in Eukaryotes

Cited by 7 publications

References 135 publications

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F₂Cross of Selectively-Bred Rats

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F₂Cross of Selectively-Bred Rats

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke

Mitochondrial tRNA^Glu 14693A > G Mutation, an “Enhancer” to the Phenotypic Expression of Leber's Hereditary Optic Neuropathy

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Output Regulation and Function Optimization of Mitochondria in Eukaryotes

Cited by 7 publications

References 135 publications

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F2Cross of Selectively-Bred Rats

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F2Cross of Selectively-Bred Rats

Transcription Factor EB: A Promising Therapeutic Target for Ischemic Stroke

Mitochondrial tRNAGlu 14693A > G Mutation, an “Enhancer” to the Phenotypic Expression of Leber's Hereditary Optic Neuropathy

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Product

Resources

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Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F₂Cross of Selectively-Bred Rats

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F₂Cross of Selectively-Bred Rats

Mitochondrial tRNA^Glu 14693A > G Mutation, an “Enhancer” to the Phenotypic Expression of Leber's Hereditary Optic Neuropathy