Osteocytes burn out, give bone a break

Abstract

The pathogenic mechanisms of chronic kidney disease-induced osteoporosis are not well understood and might involve metabolic alterations and apoptosis of osteocytes. In this issue, Hsu et al. present experimental work in uremic mice and cultured mouse osteoblasts showing that impaired mitochondrial function and mitophagy in osteocytes contribute to chronic kidney disease-associated osteoporosis. They investigate new therapeutic approaches to improve mitochondrial function in the setting of increased uremic toxin levels.

Figure 1 |. Effects of increased mitochondrial stress on bone volume and mineralization in chronic kidney disease (CKD).

Mitochondria that are damaged by stress are selectively degraded by mitophagy. During this process, mitochondria are engulfed in lysosomes, forming mitolysosomes. In CKD, uremic toxins contribute to mitochondrial damage, increased mitophagy, and altered clearance of mitolysosomes, leading to impaired osteocyte function and bone loss. This is prevented by mitochondria antioxidant mitoquinone mesylate (MitoQ) and charcoal adsorbent AST-120. The proximal molecular mechanisms that regulate mitochondrial function and mitophagy in CKD require further investigation.