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Review
. 2021 Dec 7:9:799123.
doi: 10.3389/fcell.2021.799123. eCollection 2021.

Mechanisms of FA-Phagy, a New Form of Selective Autophagy/Organellophagy

Jiayi Lu  1 , Bernard Linares  1 , Zhen Xu  1 , Yan-Ning Rui  1
Affiliations
Review

Mechanisms of FA-Phagy, a New Form of Selective Autophagy/Organellophagy

Jiayi Lu et al. Front Cell Dev Biol. .

Abstract

Focal adhesions (FAs) are adhesive organelles that attach cells to the extracellular matrix and can mediate various biological functions in response to different environmental cues. Reduced FAs are often associated with enhanced cell migration and cancer metastasis. In addition, because FAs are essential for preserving vascular integrity, the loss of FAs leads to hemorrhages and is frequently observed in many vascular diseases such as intracranial aneurysms. For these reasons, FAs are an attractive therapeutic _target for treating cancer or vascular diseases, two leading causes of death world-wide. FAs are controlled by both their formation and turnover. In comparison to the large body of literature detailing FA formation, the mechanisms of FA turnover are poorly understood. Recently, autophagy has emerged as a major mechanism to degrade FAs and stabilizing FAs by inhibiting autophagy has a beneficial effect on breast cancer metastasis, suggesting autophagy-mediated FA turnover is a promising drug _target. Intriguingly, autophagy-mediated FA turnover is a selective process and the cargo receptors for recognizing FAs in this process are context-dependent, which ensures the degradation of specific cargo. This paper mainly reviews the cargo recognition mechanisms of FA-phagy (selective autophagy-mediated FA turnover) and its disease relevance. We seek to outline some new points of understanding that will facilitate further study of FA-phagy and precise therapeutic strategies for related diseases associated with aberrant FA functions.

Keywords: autophagy; cancer; cargo receptor; focal adhesion; intracranial aneurysm; organellophagy; vascular integrity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Molecular mechanisms of FA-phagy. Focal adhesions (FAs) are simplified as protein complexes containing integrin a and ß that bind to both the extracellular matrix and intracellular paxillin protein. Filamentous actin (F-actin) comprising actin monomers are in grey and are attached to paxillin. Different cargo receptors such as NBR1 or c-Cbl, on one hand directly interact with LC3 (round blue dots associated on both sides of autophagosome), and on the other, recognize cargos such as paxillin, facilitating FA-phagy. Alternatively, paxillin can be phosphorylated at tyrosine 40 in an SRC-selective manner, which increases the binding affinity to LC3. In the cells, LC3 mainly has two forms, LC3-I and LC3-II. With the help of Atg16L complex, LC3-I is transformed to LC3-II by a lipidation process. Lipidated LC3-II is able to insert into both sides of the phagophore membrane, a well-established mechanism for autophagosome around the cargo. LC3-II on the inner side of the autophagosome will be degraded by lysosomal enzymes after enclosed autophagosome fuse with lysosome for cargo degradation.
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