Publications by authors named "N G Avadhani"

This study shows that multiple modes of mitochondrial stress generated by partial mtDNA depletion or cytochrome c oxidase disruption cause ryanodine receptor channel (RyR) dysregulation, which instigates the release of Ca in the cytoplasm of C2C12 myoblasts and HCT116 carcinoma cells. We also observed a reciprocal downregulation of IP3R channel activity and reduced mitochondrial uptake of Ca. Ryanodine, an RyR antagonist, abrogated the mitochondrial stress-mediated increase in [Ca] and the entire downstream signaling cascades of mitochondrial retrograde signaling.

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Alcohol toxicity is a significant health problem with ~3 million estimated deaths per year globally. Alcohol is metabolized to the toxic metabolite, acetaldehyde by alcohol dehydrogenase or CYP2E1 in the hepatic tissue, and also induces reactive oxygen species (ROS), which together play a pivotal role in cell and tissue damage. Our previous studies with COS-7 cells transduced with unique human CYP2E1 variants that mostly localize to either microsomes or mitochondria revealed that mitochondrially-localized CYP2E1 drives alcohol toxicity through the generation of higher levels of ROS, which has a consequent effect on cytochrome c oxidase (CcO) and mitochondrial oxidative function.

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The mitochondrial electron transport chain is a major source of reactive oxygen species (ROS) and is also a target of ROS, with an implied role in the stabilization of hypoxia-inducible factor (HIF) and induction of the AMPK pathway. Here we used varying doses of two agents, Mito-Paraquat and Mito-Metformin, that have been conjugated to cationic triphenylphosphonium (TPP) moiety to selectively target them to the mitochondrial matrix compartment, thereby resulting in the site-specific generation of ROS within mitochondria. These agents primarily induce superoxide (O) production by acting on complex I.

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Article Synopsis
  • Immunoglobulin class switch recombination (CSR) in B cells requires increased mitochondrial mass and activity, and the transcription factor Yin Yang 1 (YY1) plays a crucial role in this process.
  • Researchers found that YY1 knockout in mouse B cells led to the altered expression of 1129 genes, including 59 related to mitochondria, and YY1 was shown to bind to many of these genes directly.
  • Despite the significant effects of YY1 knockout on gene expression and DNA loop formation linked to CSR, mitochondrial functions such as mass, membrane potential, and respiration rates remained largely unaffected.
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Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with late-stage detection and poor prognosis. This emphasizes the need to identify new markers for early diagnosis and treatment. Altered mitochondrial genome (mtDNA) content in primary tumors correlates with poor patient prognosis.

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