Drp1 Modulates Mitochondrial Stress Responses to Mitotic Arrest

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2020 Mar 24

PMID 32203171

Citations 13

Authors

Aida Pena-Blanco

Manuel D Haschka

Andreas Jenner

Theresia Zuleger

Tassula Proikas-Cezanne

Andreas Villunger

Ana J Garcia-Saez

Affiliations

Soon will be listed here.

Abstract

Antimitotic drugs are extensively used in the clinics to treat different types of cancer. They can retain cells in a prolonged mitotic arrest imposing two major fates, mitotic slippage, or mitotic cell death. While the former is molecularly well characterized, the mechanisms that control mitotic cell death remain poorly understood. Here, we performed quantitative proteomics of HeLa cells under mitotic arrest induced with paclitaxel, a microtubule-stabilizer drug, to identify regulators of such cell fate decision. We identified alterations in several apoptosis-related proteins, among which the mitochondrial fission protein Drp1 presented increased levels. We found that Drp1 depletion during prolonged mitotic arrest led to strong mitochondrial depolarization and faster mitotic cell death as well as enhanced mitophagy, a mechanism to remove damaged mitochondria. Our findings support a new role of Drp1 in orchestrating the cellular stress responses during mitosis, where mitochondrial function and distribution into the daughter cells need to be coordinated with cell fate. This novel function of Drp1 in the cell cycle becomes best visible under conditions of prolonged mitotic arrest.

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