Ubiquitination of ERMES components by the E3 ligase Rsp5 is involved in mitophagy

Identification: Belgareh-Touzé, Naïma


Ubiquitination of ERMES components by the E3 ligase Rsp5 is involved in mitophagy
Naïma Belgareh-Touzé, Laetitia Cavellini and Mickaël M. Cohen
UMR8226, CNRS/UPMC, Institut de Biologie et de Physique Chimie, 75005, Paris, France
Mitochondria are highly dynamic organelles whose morphology is conditioned by a constant equilibrium between fission and fusion events. These processes are essential to control the mitochondrial morphology and are also crucial for all mitochondrial functions including oxidative phosphorylation and apoptosis. Consequently, defects in mitochondrial dynamics are associated with numerous pathologies and severe neurodegenerative syndromes.
In the yeast Saccharomyces cerevisiae, the endoplasmic reticulum-mitochondrial encounter structure (ERMES) is a marker of sites of mitochondrial division, but it is also involved in a plethora of other mitochondrial functions including phospholipid exchange and mitophagy. However, it remains unclear how these different functions are regulated.
In mammalian cells, ubiquitin has emerged as a key regulator of mitochondrial dynamics with mitofusins and Drp1 being targeted for ubiquitination by distinct ubiquitin ligases including MITOL/March5, MULAN, Huewe1 and Parkin. Ubiquitination regulates the protein levels of DRPs but most importantly plays a general role in mitochondrial quality control and mitophagy.
In yeast, the only DRP known to be ubiquitinated is the mitofusin Fzo1. Fzo1 is ubiquitinated by Mdm30, an F-box protein of the SCF (Skp1-Cullin-F-box) ubiquitin ligase complex. The SCFMdm30 ligase promotes ubiquitination and cleavage of Fzo1 to facilitate fusion of outer membranes.
We show here that Mdm34 and Mdm12, two components of ERMES, are ubiquitinated by the E3 ligase Rsp5. This ubiquitination is not involved in mitochondrial dynamics or in the distribution and turnover of ERMES. Nevertheless, the ubiquitination of Mdm34 and Mdm12 was required for efficient mitophagy. We thus report here the first identification of ubiquitinated substrates participating in yeast mitophagy.


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