Science｜线粒体双向运输分子开关：TRAK蛋白协同调控驱动蛋白与动力蛋白新机制
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TL;DR - A Science study identifies a regulatory helix in TRAK proteins as the molecular switch coordinating kinesin- and dynein-driven mitochondrial transport. The mechanism links oxidative stress to mitochondrial redistribution and may illuminate organelle-transport defects in neurological and metabolic disease.
- When the dynein regulatory helix (DRH) is closed, it blocks dynein activation and favors kinesin-driven transport toward the cell periphery; opening it activates dynein, displaces kinesin, and reverses transport.
- TRAK1 primarily promotes outward transport, whereas TRAK2 supports bidirectional movement and predominantly drives inward, perinuclear transport at steady state.
- Oxidative stress activates JNK2, which phosphorylates TRAK2 at S84, stabilizing the open DRH state and triggering dynein-mediated mitochondrial accumulation near the nucleus.
- Synthetic-cargo assays, AlphaFold2-guided mutations, and experiments with native mitochondria supported the mechanism; related autoinhibitory switches were also observed in lysosomal adaptors JIP3 and JIP4.
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Science｜线粒体双向运输分子开关：TRAK蛋白协同调控驱动蛋白与动力蛋白新机制
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TL;DR - A Science study identifies a regulatory helix in TRAK proteins as the molecular switch coordinating kinesin- and dynein-driven mitochondrial transport. The mechanism links oxidative stress to mitochondrial redistribution and may illuminate organelle-transport defects in neurological and metabolic disease.
- When the dynein regulatory helix (DRH) is closed, it blocks dynein activation and favors kinesin-driven transport toward the cell periphery; opening it activates dynein, displaces kinesin, and reverses transport.
- TRAK1 primarily promotes outward transport, whereas TRAK2 supports bidirectional movement and predominantly drives inward, perinuclear transport at steady state.
- Oxidative stress activates JNK2, which phosphorylates TRAK2 at S84, stabilizing the open DRH state and triggering dynein-mediated mitochondrial accumulation near the nucleus.
- Synthetic-cargo assays, AlphaFold2-guided mutations, and experiments with native mitochondria supported the mechanism; related autoinhibitory switches were also observed in lysosomal adaptors JIP3 and JIP4.