Cell Reports | 朱金伟/符传孩/林霖团队合作揭示线粒体动力学调控新机制：钙调蛋白变构激活INF2驱动线粒体分裂

TL;DR - A Cell Reports paper from Shanghai Jiao Tong (Zhu Jinwei/Lin Lin), Soochow (Zhang Meng), and USTC (Fu Chuanhai) teams shows that Ca²⁺-bound calmodulin allosterically activates the formin INF2 to drive actin-dependent mitochondrial fission. It defines a CaM–INF2 signaling axis linking local calcium signals to organelle dynamics and to INF2-linked neuropathy (CMT) and kidney disease (FSGS). Note: this is a molecular/structural biology study, not an AI advance.

• Ca²⁺-CaM binds the INF2 DID domain with nanomolar affinity; a crystal structure of the DID–Ca²⁺-CaM complex reveals an atypical dual-interface mode engaging both the αN helix and the armadillo repeat (ARR) domain, unlike canonical CaM targets.
• Activation is allosteric rather than purely competitive: CaM induces DID rearrangement that disrupts DID–DAD autoinhibition, freeing the FH1-FH2 catalytic core for F-actin assembly — filling a gap since INF2 lacks classic Rho GTPase regulation.
• In cells, boosting CaM signaling enhanced ER-localized INF2-driven actin remodeling, shortening mitochondria and increasing fission; CaM-binding-deficient INF2 mutants were unresponsive to calcium stimulation.
• The CMT-associated mutation INF2 R91G strengthens Ca²⁺-CaM binding, causing excessive actin assembly and mitochondrial over-fission, suggesting a gain-of-function disease mechanism.