Ask about this productRelated genes to: POLG2 Blocking Peptide
- Gene:
- POLG2 NIH gene
- Name:
- DNA polymerase gamma 2, accessory subunit
- Previous symbol:
- -
- Synonyms:
- MTPOLB, HP55
- Chromosome:
- 17q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-16
- Date modifiied:
- 2016-07-11
Related products to: POLG2 Blocking Peptide
Related articles to: POLG2 Blocking Peptide
- Mitochondria have emerged as key regulators of breast cancer stem cell (CSC) biology. Mitochondrial metabolic pathways, including oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis, are frequently altered during tumorigenesis, highlighting their role in breast cancer pathogenesis. Since breast CSCs are highly dependent on mitochondrial metabolism, targeting mitochondrial DNA (mtDNA) replication may represent a strategy to impair CSC maintenance. Mitochondrial DNA polymerase-γ (POLG), composed of a catalytic subunit encoded by POLG1 and an accessory subunit encoded by POLG2, is essential for mtDNA replication and repair. In this pilot study, we investigated whether targeting POLG could modulate breast CSC activity. Genetic knockdown of POLG1 and POLG2 in MCF-7 cells resulted in mtDNA depletion, reduced mitochondrial protein expression, impaired energy production, and loss of stemness-related features. To pharmacologically target POLG, we tested Alovudine, a nucleoside reverse transcriptase inhibitor known to act as an off-target POLG inhibitor. In MCF-7 cells, Alovudine reduced clonogenic potential, decreased mitochondrial DNA-encoded protein levels, and lowered oxygen consumption. To further validate these findings, we employed the independent POLG inhibitor Zalcitabine (ddC) in additional breast cancer models. ddC impaired mitochondrial respiration, reduced mammosphere formation, and modulated SOX2 and NANOG expression. Preliminary Kaplan-Meier analyses in a cohort of 458 breast cancer patients showed that high POLG1 expression correlates with worse clinical outcomes, including relapse-free and overall survival. Taken together, these findings suggest that POLG supports mitochondrial function and CSC maintenance, highlighting its potential as a therapeutic target and prognostic biomarker in breast cancer. - Source: PubMed
Publication date: 2026/08/08
Chinigò ChiaraSugden Conor JFiorillo MarcoCappello Anna RitaSotgia FedericaLisanti Michael P - Sex differences in lifespan and age-associated phenotypes are pervasive across species, yet the mechanisms remain poorly understood. Mitochondrial dysfunction is a major hallmark of aging, but whether skeletal muscle mitochondria age along sex specific trajectories remains incompletely defined. - Source: PubMed
Publication date: 2026/04/29
Holcom AngelinaLiao AshleyHolden Kaitlyn GBronikowski Anne MWebb Ashley E - Silver nanoparticles (AgNPs) are engineered nanomaterials composed of silver atomic clusters with sizes ranging from 1 to 100 nm. These particles have gained widespread application in food and medicine due to their potent broad-spectrum antibacterial properties. As research on AgNPs has advanced, increasing attention has focused on their cytotoxic mechanisms, particularly the phenomenon of mitochondrial targeting and subsequent cellular damage. However, the precise molecular pathways underlying these effects remain incompletely elucidated. In the present study, HeLa cells were exposed to 15 nm AgNPs for 24 h. Cell viability assays revealed a concentration-dependent decrease in survival when AgNP concentrations reached 16 µg/mL. Notably, reverse transcription polymerase chain reaction (RT-PCR) analysis demonstrated unchanged expression levels of the POLG2 gene, which encodes the accessory subunit (Polg2) of mitochondrial DNA polymerase gamma (Pol-γ). This observation suggests preserved nuclear integrity under these experimental conditions. Concomitant with these findings, quantitative analysis of mitochondrial DNA (mtDNA) content showed a significant increase in mtDNA copy number, implying compensatory mitochondrial proliferation secondary to damage. Further mechanistic investigation through immunoprecipitation assays revealed direct physical interaction between AgNPs and the Polg2 protein. Collectively, these results support a model wherein AgNP-induced mitochondrial dysfunction but not nuclear damage in cytotoxic pathways. The observed AgNP-Polg2 interaction emerges as a critical factor in disrupting mitochondrial homeostasis, suggesting novel therapeutic targets for mitigating nanoparticle toxicity. We propose that after entering cells, AgNPs directly interact with mitochondrial DNA polymerase, thereby disrupting mitochondrial homeostasis and ultimately leading to cell death. - Source: PubMed
Publication date: 2026/04/07
Peng XuelingLiu Qingdai - N6-methyladenosine (m6A) modification is the most prevalent posttranscriptional epigenetic modification in mammalian mRNAs, and it has been implicated in the regulation of nervous system development by modulating mRNA metabolism. VIRMA is the largest core subunit of the m6A methyltransferase complex and is essential for the assembly and stability of the m6A methyltransferase complex. In the retina, m6A methylation modification is widely distributed in various cellular layers and is essential for retinal homeostasis. Here, we demonstrate that VIRMA-mediated m6A modification is essential for retinal homeostasis. Loss of Virma in retinal rod cells resulted in abnormal reduction in m6A methylation levels, along with impaired photoreceptor function and degeneration. Mechanically, Virma depletion in photoreceptors dampened the m6A modification level of visual perception-associated genes, resulting compromised visual function and photoreceptors degeneration. Moreover, Virma interacted with splicing factor to regulate the alternative splicing events of retina function-related genes such as Polg2, which contributes to photoreceptor damage. Reintroduction of normal Virma expression colonially rescued photoreceptor degeneration. Collectively, our data elucidate the important role of Virma-mediated m6A modification in photoreceptor function and suggest that epigenetic modulation could serve as a potential target to treat these blinding diseases. - Source: PubMed
Publication date: 2026/03/19
Liu WenjingWu XiaojingZou RongZhang FanFan YudiSun KuanxiangYang LipingHu JiangZhang LinZhu Xianjun - - Source: PubMed
Publication date: 2026/01/30
Koch Christian ATüttelmann FrankVedanarayanan Vetta