In the study published in the journal Nature Cell Biology on May 22, 2023, entitled Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes, Prof. SHAO Mengle’s group at the Shanghai Institute of Immunity and Infection of the Chinese Academy of Sciences, and Prof. GAN Zhenji at Medical School of Nanjing University reported their new research.
As is well known to all, mitochondria are the energy factories of the cell. At the same time, they are also the center of cellular metabolism, natural immunity and apoptosis control. Mitochondria are extensively involved in numerous cell biological processes. Therefore, the maintenance of normal mitochondrial function requires a fine-grained, multi-layered quality control system.
Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity and acting as both protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switching.
Here Prof. SHAO’s group reported that cold-responsive mitochondrial proteolysis is a prerequisite for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. Thermogenic stimulation selectively promotes mitochondrial proteostasis in mature white adipocytes via the mitochondrial protease LONP1. Disruption of LONP1-dependent proteolysis substantially impairs cold- or β3 adrenergic agonist-induced white-to-beige identity switching of mature adipocytes.
Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming.
Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity.
Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.
Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes. (Image by SIII)
Contact
SHAO Mengle
Shanghai Institute of Immunity and Infection, CAS
E-mail: mlshao@siii.cas.cn
Reference: https://www.nature.com/articles/s41556-023-01155-3
