This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: The Intracellular Quality Control Project at the Tokyo Metropolitan Institute of Medical Science has identified a molecular mechanism that helps initiate the formation of autophagic membranes around damaged mitochondria. The study reveals that the small GTPases RAB1A and RAB1B act as molecular links between OPTN, an autophagy adaptor, and ATG9A vesicles, which contribute to the initial formation of autophagic membranes during mitophagy (mitochondria selective autophagy).
By recruiting ATG9A vesicles to damaged mitochondria, the OPTN–RAB1 pathway helps establish the site where the autophagic membrane begins to form. The findings are published in Autophagy. Mitochondria are essential organelles that produce energy and perform numerous functions required for cell survival.
However, damaged mitochondria can become harmful to cells and therefore need to be selectively eliminated. Cells accomplish this through mitophagy, a form of selective autophagy that recognizes and removes damaged mitochondria. One of the best-characterized mitophagy pathways is controlled by the kinase PINK1 and the E3 ubiquitin ligase Parkin.
When mitochondria are damaged, PINK1 and Parkin promote the accumulation of ubiquitin on the mitochondrial surface. This ubiquitin signal is recognized by autophagy adaptors such as OPTN (optineurin), which connect damaged mitochondria to the autophagy machinery. However, an important question has remained: How does an autophagy adaptor such as OPTN initiate the formation of an autophagic membrane around the damaged mitochondria?
The research group previously found that OPTN recruits ATG9A vesicles to damaged mitochondria. ATG9A vesicles are thought to provide membrane seeds and function as important components in the early stages of autophagosome formation. This finding suggested that autophagy adaptors may have a role beyond simply connecting damaged mitochondria to the autophagic machinery.
They may also actively recruit the membrane components required to initiate autophagic membrane formation. The molecular mechanism responsible for this recruitment, however, remained unclear. In the present study, the researchers investigated how OPTN recruits ATG9A vesicles during PINK1-Parkin-mediated mitophagy.
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