AutophagySep 2, 2026

RAB1 helps OPTN control damaged mitochondria removal by bringing in ATG9A

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 3, 2026

Abstract

RAB1A and RAB1B are essential for the recruitment of ATG9A vesicles to damaged mitochondria during mitophagy.

Damaged mitochondria undergo selective elimination through a process called mitophagy.
PINK1 and PRKN/Parkin are involved in amplifying signals that mark damaged mitochondria for degradation.
OPTN plays a crucial role in connecting ubiquitinated mitochondria with the necessary components for autophagy.
RAB1A and RAB1B directly bind to the OPTN leucine zipper domain, highlighting a new interaction in mitophagy.
Knockdown of RAB1A and RAB1B disrupts the assembly of OPTN at sites where new phagophores form, hindering mitophagy.
RAB1A and RAB1B associate with ATG9A vesicles through a specific modification, facilitating their tethering to damaged mitochondria.

Simplified

Damaged mitochondria are selectively eliminated through mitophagy, a critical quality control process. A kinase PINK1 and an E3 ubiquitin ligase PRKN/Parkin, both of which are mutated in familial Parkinson disease, amplify ubiquitin signals on the damaged mitochondria. The autophagy receptor OPTN plays a pivotal role in mitophagy by bridging ubiquitinated mitochondria with autophagy components. Although OPTN is known to recruit ATG9A-positive vesicles to facilitate mitophagy progression, the precise molecular mechanisms governing this recruitment remain poorly understood. In this study, we identify the small RAB GTPases RAB1A and RAB1B as direct binding partners of the OPTN leucine zipper (LZ) domain. We demonstrate that RAB1A/1B is required for the recruitment of ATG9A vesicles to mitochondria during the initial stages of mitophagy. Knockdown of RAB1A and RAB1B significantly impaired the assembly of OPTN at phagophore formation sites, leading to a profound inhibition of mitophagy progression. Mechanistically, we found that RAB1A/1B associate with ATG9A-positive vesicles via their C-terminal prenylation, thereby tethering these vesicles to the OPTN-bound mitochondria. Our findings establish a novel OPTN-RAB1-ATG9A axis that drives the de novo synthesis of phagophore membranes in close proximity to damaged mitochondria. This work clarifies how selective autophagy receptors spatially coordinate membrane trafficking to ensure the efficient clearance of dysfunctional organelles.

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RAB1 helps OPTN control damaged mitochondria removal by bringing in ATG9A

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