Mitochondrial heterogeneity disrupts osteoclast differentiation and bone resorption by impairing respiratory complex I

Mitochondrial heteroplasmy in mice impairs osteoclast differentiation and bone resorption by reducing mitochondrial localization of respiratory complex I subunits, disrupting ATP production.

• Why it matters: Poor bone health and bone structure defects in heteroplasmic patients are linked to mitochondrial mutations, but the underlying mechanism has been hard to test in vivo.
• What they did: Using a heteroplasmic mouse model, the study assessed osteoclast differentiation and mitochondrial complex I localization, then tested whether spermidine could restore mitochondrial health and autophagic flux.
• The result: Autophagic flux is exhausted in heteroplasmic settings, and spermidine rescues osteoclast activity in mice and in patient-derived cells, suggesting a potential modulator for human mitochondrial heteroplasmy.

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