Mitochondrial regulation of obesity by POMC neurons

Biochim Biophys Acta Mol Basis Dis. 2025 Jan 19:167682. doi: 10.1016/j.bbadis.2025.167682. Online ahead of print.

Abstract

Pro-opiomelanocortin (POMC) neurons, nestled in the hypothalamus, play a pivotal role in the intricate coordination of energy homeostasis and metabolic pathways. These neurons' mitochondria, often hailed as the cell's powerhouses, are crucial for maintaining cellular energy equilibrium and metabolic functionality. Recent research has illuminated the complex interplay between mitochondrial dynamics and POMC neuronal activity, underscoring their critical involvement in the pathogenesis of a spectrum of metabolic disorders, notably obesity and diabetes. This comprehensive review delves into the molecular mechanisms that underlie how mitochondrial function within POMC neurons modulates metabolic regulation. We dissect the impact of mitochondrial dynamics, encompassing fusion, fission, mitophagy, and biogenesis, on the regulation of POMC neuronal activity. Furthermore, we scrutinize the role of mitochondrial dysfunction in POMC neurons in the etiology of obesity, identifying key therapeutic targets within these pathways. We offer an in-depth perspective on the indispensable role of POMC neuronal mitochondria in metabolic regulation and chart future research directions to bridge the existing knowledge gaps in this field.

Keywords: Metabolic regulation; Mitochondrion; Obesity; POMC.

Publication types

  • Review