Contact-phagy remodels ER-mitochondria contact sites

Contact-phagy selectively remodels ER-mitochondria contact-site subdomains by using SIGMAR1–CCPG1 nanoclusters to initiate turnover, linked to mitochondrial fission via MFF and DRP1.

• Why it matters: Interorganelle ER-mitochondria interfaces must be selectively removed during metabolic or mitochondrial stress, but the mechanisms that target specific ERMCS subdomains were unclear.
• What they did: The authors identify an ER-phagy receptor complex where ER-resident SIGMAR1 associates with CCPG1, and SIGMAR1–CCPG1 nanoclusters mark ERMCS autophagy initiation sites. They show Contact-phagy is triggered by metabolic and mitochondrial stress and that CCPG1 or SIGMAR1 loss disrupts DRP1/MFF dynamics and mitochondrial remodeling.
• The result: Contact-phagy promotes turnover of defined contact-site components without broadly impacting general ER-phagy, mitophagy, or bulk autophagy, and CCPG1 loss disrupts ER-mitochondria organization and mitochondrial function in pancreatic tissue. In pancreatic cancer cells, CCPG1 and SIGMAR1 are required for organelle integrity and bioenergetic capacity.

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