韩国首尔国立大学Yun-Sil Lee团队近期取得重要研究进展，他们研究发现线粒体碎裂能增强线粒体分泌以促进成骨。这一研究成果2023年2月7日在线发表于《细胞—代谢》杂志上。

据介绍，在骨基质中大量检测到线粒体成分，这意味着它们以某种方式被运输到细胞外以调节成骨。

研究人员发现，线粒体和线粒体来源囊泡（MDV）是从成熟的成骨细胞分泌的，以促进骨祖细胞的分化。成骨诱导通过CD38/cADPR信号刺激线粒体断裂、圆环形成和线粒体分泌。通过Opa1敲低或Fis1过表达增强线粒体分裂和圆环形成，增加线粒体分泌并加速成骨。研究人员还表明，诱导Opa1表达的线粒体融合启动子M1阻碍成骨，而成骨细胞特异性Opa1缺失增加骨量。分泌线粒体和MDV促进体内骨再生。

总之，这一发现表明，成熟成骨细胞的线粒体形态适合细胞外分泌，分泌的线粒体和MDV是成骨的关键推动者。

附：英文原文

Title: Mitochondrial fragmentation and donut formation enhance mitochondrial secretion to promote osteogenesis

Author: Joonho Suh, Na-Kyung Kim, Wonn Shim, Seung-Hoon Lee, Hyo-Jeong Kim, Eunyoung Moon, Hiromi Sesaki, Jae Hyuck Jang, Jung-Eun Kim, Yun-Sil Lee

Issue&Volume: 2023/02/07

Abstract: Mitochondrial components have been abundantly detected in bone matrix, implying that they are somehow transported extracellularly to regulate osteogenesis. Here, we demonstrate that mitochondria and mitochondrial-derived vesicles (MDVs) are secreted from mature osteoblasts to promote differentiation of osteoprogenitors. We show that osteogenic induction stimulates mitochondrial fragmentation, donut formation, and secretion of mitochondria through CD38/cADPR signaling. Enhancing mitochondrial fission and donut formation through Opa1 knockdown or Fis1 overexpression increases mitochondrial secretion and accelerates osteogenesis. We also show that mitochondrial fusion promoter M1, which induces Opa1 expression, impedes osteogenesis, whereas osteoblast-specific Opa1 deletion increases bone mass. We further demonstrate that secreted mitochondria and MDVs enhance bone regeneration in vivo. Our findings suggest that mitochondrial morphology in mature osteoblasts is adapted for extracellular secretion, and secreted mitochondria and MDVs are critical promoters of osteogenesis.

DOI: 10.1016/j.cmet.2023.01.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00003-7