# Cyclic stretch induces autophagy-mediated focal adhesion remodeling and activates mitochondria

## TL;DR

This study shows how mechanical strain causes cells to reorganize their structure through autophagy and mitochondrial activity.

## Contribution

The paper identifies autophagy-mediated focal adhesion remodeling and mitochondrial activation as key mechanisms in cellular adaptation to mechanical stress.

## Key findings

- Cyclic stretch induces autophagy and actin fiber reorientation in smooth muscle cells.
- Autophagy inhibition delays actin reorientation and reduces focal adhesion remodeling.
- Mitochondrial activation supports the cellular response to mechanical strain.

## Abstract

The study reveals molecular details of cellular adaptation to mechanical strain involving autophagy-mediated focal adhesion remodeling and mitochondrial activation.

Mammalian cells are continuously exposed to internally generated or externally applied mechanical stimuli. Mechanosensitive proteins enable cells to sense mechanical stress and induce protective mechanisms like autophagy and cytoskeletal reorientation. However, how these contribute to cellular and tissue adaptations remains largely unknown. Here, we studied the response of rat smooth muscle cells (A7r5) to uniaxial cyclic stretch. Stretching induced autophagy and adaptive actin fiber reorientation. Inhibiting autophagy using chloroquine or expressing a Bag3 (T285D-S289D) phosphosite mutant that impairs chaperone-assisted selective autophagy (CASA) delayed reorientation. Proteomic analysis revealed a depletion of cytoskeletal and focal adhesion proteins after stretching, which was attenuated by autophagy inhibition. Stretching caused a reduction in focal adhesion (FA) size, and the remodeled FAs reoriented perpendicularly to the strain direction. Concurrently, prolonged stretching activated mitochondria, and inhibiting mitochondrial ATP synthesis slowed actin reorientation, suggesting that mitochondrial activity supports the mechanoresponse. Our findings highlight the role of autophagy and mitochondria in the structural remodeling of cells upon adaptation to mechanical stress.