Patients with primary mitochondrial disease manifesting cardiomyopathy are twice as likely to die compared to those without cardiomyopathy. Here, the authors show that a modest increase in cardiac mit...

Aged HSF1 muscle-specific knockout mice show deteriorated muscle atrophy and metabolic dysfunction, while active HSF1 overexpression improves muscle function via activating SIRT3 to deacetylate both ...

Thyroid hormone receptor β1 (TRβ) downregulation correlates with poor prognosis in clear cell renal cell carcinoma (ccRCC). Restoration of TRβ and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha suppresses tumor progression in ccRCC through Uncoupling protein 1 mediated tumor cell “slimming” and optic atrophy 1/mitofusin 2 dependent mitochondrial fusion. Abstract The abnormal accumulation of lipids is a hallmark of clear cell renal cell carcinoma (ccRCC). Both the thyroid hormone receptor β1 (TRβ) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) are key regulators of mitochondrial function and lipid metabolism. However, their specific interaction and influence on ccRCC development and lipid accumulation remain poorly understood. This study identified genes jointly regulated by TRβ and PGC1α, which are implicated in lipid browning and mitochondrial fusion. Mechanistically, T3-activated TRβ interacts with PGC1α to transcriptionally upregulate PGC1α, UCP1, and mitochondrial fusion genes OPA1 and MFN2, thereby enhancing mitochondrial activity, promoting lipid utilization, and suppressing ccRCC progression. These results indicate that the mitochondrial and metabolic effects of TRβ in ccRCC are mediated through PGC1α expression and function. Activation of the TRβ/PGC1α through hormonal and pharmacological means may offer a promising therapeutic approach for ccRCC.

Microplastics (MPs) have emerged as hazardous substances, eliciting widespread concern regarding their potential toxicity. Although our previous resea…

Cell Death & Disease - Secreted spermidine synthase reveals a paracrine role for PGC1α-induced growth suppression in prostate cancer

Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during c...

Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during c...

Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during c...

Xu et al. show that IL6, not TNF-α, suppresses mitochondrial function. When PGC1 is low, IL6 increases HIF1A transcription and stabilizes HIF1α protein via ERRα. HIF1α reciprocally suppresses ERRα, co...

Dumesic et al. identify RBM43 as an RNA-binding protein that governs mitochondrial biogenesis through suppression of PGC1α translation. RBM43 is induced by inflammatory signaling and controls a diabetogenic regulatory axis in adipocytes whereby decreased…