VPS13D promotes peroxisome biogenesis

Heather A Baldwin; Chunxin Wang; Gil Kanfer; Hetal V Shah; Antonio Velayos-Baeza; Marija Dulovic-Mahlow; Norbert Brüggemann; Allyson Anding; Eric H Baehrecke; Dragan Maric; William A Prinz; Richard J Youle

doi:10.1083/jcb.202001188

VPS13D promotes peroxisome biogenesis

J Cell Biol. 2021 May 3;220(5):e202001188. doi: 10.1083/jcb.202001188.

Authors

Heather A Baldwin^{1

2}, Chunxin Wang¹, Gil Kanfer¹, Hetal V Shah^{1

3}, Antonio Velayos-Baeza⁴, Marija Dulovic-Mahlow⁵, Norbert Brüggemann^{5

6}, Allyson Anding⁷, Eric H Baehrecke⁷, Dragan Maric⁸, William A Prinz⁹, Richard J Youle¹

Affiliations

¹ Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
² Cell, Molecular, Developmental Biology and Biophysics Doctoral Program, Johns Hopkins University, Baltimore, MD.
³ Program in Neuroscience & Cognitive Science, University of Maryland, College Park, MD.
⁴ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
⁵ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
⁶ Department of Neurology, University of Lübeck, Lübeck, Germany.
⁷ Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA.
⁸ National Institute of Neurological Disorders and Stroke Flow Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
⁹ Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.

Abstract

The VPS13 gene family consists of VPS13A-D in mammals. Although all four genes have been linked to human diseases, their cellular functions are poorly understood, particularly those of VPS13D. We generated and characterized knockouts of each VPS13 gene in HeLa cells. Among the individual knockouts, only VPS13D-KO cells exhibit abnormal mitochondrial morphology. Additionally, VPS13D loss leads to either partial or complete peroxisome loss in several transformed cell lines and in fibroblasts derived from a VPS13D mutation-carrying patient with recessive spinocerebellar ataxia. Our data show that VPS13D regulates peroxisome biogenesis.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

HEK293 Cells
HeLa Cells
Humans
Mitochondria / genetics
Mitochondria / metabolism
Mutation / genetics
Peroxisomes / genetics*
Peroxisomes / metabolism*
Proteins / genetics*
Proteins / metabolism*

Substances

Proteins
VPS13D protein, human

Grants and funding

R35 GM131689/GM/NIGMS NIH HHS/United States