# The ubiquitin E3 ligase TRIM27 emerges as a new player in mitophagy

## TL;DR

This paper identifies TRIM27 as a new ubiquitin E3 ligase involved in a PINK1-PRKN-independent mitophagy pathway, offering an alternative mechanism for removing damaged mitochondria.

## Contribution

The study introduces TRIM27 as a novel player in ubiquitin-dependent mitophagy independent of the PINK1-PRKN pathway.

## Key findings

- TRIM27 participates in PINK1-PRKN-independent mitophagy.
- TRIM27 works with SQSTM1/p62 and TBK1 to cluster mitochondria and enhance mitophagy.
- A TRIM27-SQSTM1/p62-TBK1 pathway is proposed as an alternative mitophagy mechanism.

## Abstract

Mitochondria are the center for energy production, cell fate determination and synthesis of essential biomolecules in cells. Hence, mitochondrial quality control mechanisms are essential for cellular health. Failure of these control mechanisms may lead to damaged mitochondria that represent a threat to cell survival. Mitophagy is a selective autophagy process that removes damaged mitochondria through lysosomal degradation. The triggering of mitophagy can be either ubiquitin dependent or ubiquitin independent. Ubiquitin-dependent mitophagy relies on ubiquitin as a signal on the surface of dysfunctional mitochondria. PRKN/PARKIN is the ubiquitin E3 ligase of the well described PINK1-PRKN-dependent mitophagy. However, other ubiquitin-dependent mitophagy pathways that are independent of PRKN are emerging, but little is known about which ubiquitin E3 ligases are implicated. We shall here discuss our recent identification of the ubiquitin E3 ligase TRIM27 (tripartite motif containing 27) as a player in PINK1-PRKN-independent mitophagy. We will focus on the concerted action of TRIM27, the autophagy receptor SQSTM1/p62 and TBK1 (TANK binding kinase 1), which leads to mitochondrial clustering and enhanced mitophagy. We propose a model where a TRIM27-SQSTM1/p62-TBK1 pathway acts as an alternative or compensatory pathway for the PINK1-PRKN pathway to induce ubiquitin-dependent mitophagy.