Pena-Blanco, Aida, Haschka, Manuel D., Jenner, Andreas, Zuleger, Theresia, Proikas-Cezanne, Tassula, Villunger, Andreas and Garcia-Saez, Ana J. (2020). Drp1 modulates mitochondrial stress responses to mitotic arrest. Cell Death Differ., 27 (9). S. 2620 - 2635. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5403

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pena-Blanco, AidaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haschka, Manuel D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jenner, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zuleger, TheresiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Proikas-Cezanne, TassulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villunger, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Saez, Ana J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-340601
DOI: 10.1038/s41418-020-0527-y
Journal or Publication Title: Cell Death Differ.
Volume: 27
Number: 9
Page Range: S. 2620 - 2635
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5403
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CYTOCHROME-C; CELL-CYCLE; FISSION PROTEIN; GENE ONTOLOGY; APOPTOSIS; CANCER; BAX; PHOSPHORYLATION; DEGRADATION; CHECKPOINTMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34060

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