VPS13D promotes peroxisome biogenesis

Author:

Baldwin Heather A.12ORCID,Wang Chunxin1ORCID,Kanfer Gil1ORCID,Shah Hetal V.13,Velayos-Baeza Antonio4ORCID,Dulovic-Mahlow Marija5,Brüggemann Norbert56ORCID,Anding Allyson7ORCID,Baehrecke Eric H.7ORCID,Maric Dragan8,Prinz William A.9ORCID,Youle Richard J.1ORCID

Affiliation:

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.

Funder

National Institute of Neurological Disorders and Stroke

Publisher

Rockefeller University Press

Subject

Cell Biology

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