Changes in Mitochondrial Morphology and Bioenergetics in Human Lymphoblastoid Cells With Four Novel OPA1 Mutations

Investigative Ophthalmology & Visual Science
Shu-Huei KaoAn-Lo Lin

Abstract

Mutations in the optic atrophy 1 gene (OPA1) have been reported in patients with autosomal dominant optic atrophy (ADOA). OPA1 plays important roles in mitochondrial dynamics and cell apoptosis. The link between OPA1 mutations and changes in bioenergetics is still not fully resolved. The aim of this study was to investigate the effects of OPA1 mutations on the mitochondrial tubular network and bioenergetics. We established lymphoblastoid cell lines from four ADOA families harboring different OPA1 mutations, unaffected relatives (internal control cell lines), and unrelated normal controls (normal control cell lines). OPA1 splice variants and mRNA were analyzed by reverse transcription-PCR and quantitative real-time PCR. Protein isoforms were examined by Western blotting. The mitochondrial network was visualized by confocal microscopy. Mitochondrial bioenergetics were assessed using a Seahorse XF24 flux analyzer. Mitochondrial membrane potential and oxidative damage were analyzed by flow cytometry. OPA1 mutant cell lines showed significant decreases in OPA1 mRNA and protein expression, mitochondrial membrane potential, and ATP synthesis. A marked deficiency of the long isoform of OPA1 was observed in cells with OPA1 mutations in ...Continue Reading

Citations

Mar 16, 2017·AAPS PharmSciTech·Avadhesh Singh KushwahaS Narasimha Murthy
Aug 25, 2017·Scientific Reports·Valentina Di PietroAntonio Belli
Nov 26, 2015·The Journal of Biological Chemistry·Zachary C RyanRajiv Kumar
Jun 21, 2020·Investigative Ophthalmology & Visual Science·Shanshan SunMarcela Votruba
Feb 22, 2021·The International Journal of Biochemistry & Cell Biology·Tharsini NavaratnarajahFelix Distelmaier
Jun 17, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Pauline RobertLaurent Loufrani
Jun 29, 2021·Frontiers in Neurology·Valentina Del Dotto, Valerio Carelli
Oct 23, 2021·Frontiers in Cell and Developmental Biology·Xiao-Hui ZhangShi-Hui Wei

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