A thermosensitive TET-Parkin epigenetic axis couples mitochondrial quality control to adaptive thermogenesis in adipose tissue.

Adipose tissue thermogenesis is a major determinant of energy homeostasis, and its dysregulation contributes to obesity and metabolic disease. Parkin-mediated mitophagy is required for thermogenic adaptation, but the upstream mechanisms linking thermal cues to this pathway remain poorly defined. Here, we identify the ten-eleven translocation (TET) family of DNA dioxygenases as thermosensitive epigenetic regulators of Prkn transcription in adipocytes. Cold exposure coordinately suppressed TET expression and reduced global 5-hydroxymethylcytosine (5hmC) levels in white and brown adipose tissue through β-adrenergic signaling. Adipose-specific TET triple-knockout mice exhibited enhanced white fat beiging, brown fat activation, increased energy expenditure, and improved cold tolerance. Transcriptomic network analysis identified Parkin as a key mitophagy node in TET-deficient adipose tissue. Consistent with this, loss of adipose TET reduced Parkin expression, impaired mitophagic flux, and promoted accumulation of metabolically active mitochondria with increased respiratory capacity. Mechanistically, TET proteins occupied the Prkn promoter and maintained a transcriptionally permissive state through catalytic conversion of 5-methylcytosine to 5hmC, whereas TET loss increased promoter methylation and suppressed Prkn expression. Re-expression of wild-type, but not catalytically inactive, Parkin largely normalized mitochondrial content and respiratory activity in TET-deficient adipocytes. Together, these findings define a thermosensitive TET-Parkin epigenetic axis that links environmental cold signals to mitochondrial quality control during adaptive thermogenesis.