RGS12 is required for the maintenance of mitochondrial function during skeletal development

Gongsheng Yuan; Shuting Yang; Min Liu; Shuying Yang

doi:10.1038/s41421-020-00190-w

RGS12 is required for the maintenance of mitochondrial function during skeletal development

Cell Discov. 2020 Sep 1:6:59. doi: 10.1038/s41421-020-00190-w. eCollection 2020.

Authors

Gongsheng Yuan¹, Shuting Yang¹, Min Liu¹, Shuying Yang^{1

2

3}

Affiliations

¹ Department of Basic and Translational Sciences, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA USA.
² The Penn Center for Musculoskeletal Disorders, University of Pennsylvania, School of Medicine, Philadelphia, PA USA.
³ Center for Innovation & Precision Dentistry, University of Pennsylvania, School of Dental Medicine, School of Engineering and Applied Sciences, Philadelphia, PA USA.

Abstract

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.

Keywords: Ageing; Mechanisms of disease.

Abstract

Grants and funding