RGS12 is required for the maintenance of mitochondrial function during skeletal development.
Gongsheng YuanShuting YangMin LiuShuying YangPublished in: Cell discovery (2020)
Mitochondrial morphology and function are crucial for tissue homeostasis, such as for skeletal development, but the cellular and molecular mechanisms remain unclear. Here, we provide evidence that regulator of G-protein signaling 12 (RGS12) is present in the mitochondria of primary chondrocytes and cartilage tissues. Deletion of RGS12 in type II collagen-positive cells led to a significant decrease in mitochondrial number, membrane potential, and oxidative phosphorylation function. Mechanistically, RGS12 promoted the function of ATP5A as an enhancer of tyrosine phosphorylation. Mice with RGS12 deficiency in the chondrocyte lineage showed serious body retardation, decreased bone mass, and chondrocyte apoptosis due to the defective activity of ATP synthase. To our knowledge, this is the first report that RGS12 is required for maintaining the function of mitochondria, which may allow it to orchestrate responses to cellular homeostasis.
Keyphrases
- oxidative stress
- cell death
- cell cycle arrest
- transcription factor
- induced apoptosis
- healthcare
- gene expression
- extracellular matrix
- endoplasmic reticulum stress
- metabolic syndrome
- protein kinase
- bone mineral density
- adipose tissue
- type diabetes
- signaling pathway
- postmenopausal women
- reactive oxygen species
- risk assessment
- human health
- high fat diet induced