# The conserved outer mitochondrial membrane protein Mtch regulates mitophagy during Drosophila intestinal development

## TL;DR

This study identifies Mtch as a new regulator of mitophagy in fruit fly intestinal cells, showing its role in regulating the insertion of a key mitophagy receptor.

## Contribution

The study reveals Mtch as a novel regulator of mitophagy by linking it to the insertion of the BNIP3 receptor during intestinal development in Drosophila.

## Key findings

- Mtch mutant cells fail to clear mitochondria and show elevated autophagy markers.
- Mtch functions in a mitophagy pathway with Vps13D, PINK1, Parkin, and BNIP3.
- Mtch is required for proper expression of the tail-anchored mitophagy receptor BNIP3.

## Abstract

The clearance of mitochondria by autophagy (mitophagy) is important for cell health. Mutations in genes that are required for mitophagy, including Vps13D, PINK1, and Parkin, are associated with movement disorders, but gaps exist in our understanding of how Vps13D regulates mitophagy. Here, we identify Mtch (MTCH2 in humans) as a regulator of mitophagy based on a relationship with Vps13D during developmentally programmed mitophagy in Drosophila intestine enterocyte cells. Similar to Vps13D mutant cells, Mtch mutant cells fail to clear mitochondria and possess elevated markers of autophagy. Genetic and molecular experiments reveal that Mtch and Vps13D function in a mitophagy pathway with PINK1, Parkin, and the mitophagy receptor BNIP3. Unlike Vps13D and Parkin mutant cells, Mtch is required for proper expression of the tail-anchored protein BNIP3. Thus, the tail-anchored protein insertase function of Mtch/MTCH2 likely explains how these proteins possess multiple cell context-specific functions.

Mitophagy is critical for cellular health and is associated with multiple diseases. This study shows that the outer mitochondrial membrane protein Mtch functions as a novel regulator of mitophagy during Drosophila intestinal development, likely by regulating the insertion of the mitophagy receptor BNIP3.