BACE1 Inhibition Increases Susceptibility to Oxidative Stress by Promoting Mitochondrial Damage

Carolina Francelin; Sayak K. Mitter; Qingwen Qian; Sandeep Kumar Barodia; Colin Ip; Xiaoping Qi; Hongmei Gu; Judith Quigley; Matthew S. Goldberg; Maria B. Grant; Michael E. Boulton

doi:10.3390/antiox10101539

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BACE1 Inhibition Increases Susceptibility to Oxidative Stress by Promoting Mitochondrial Damage

Journal article

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BACE1 Inhibition Increases Susceptibility to Oxidative Stress by Promoting Mitochondrial Damage

Carolina Francelin, Sayak K. Mitter, Qingwen Qian, Sandeep Kumar Barodia, Colin Ip, Xiaoping Qi, Hongmei Gu, Judith Quigley, Matthew S. Goldberg, Maria B. Grant, …

Antioxidants, Vol.10(10), p.1539

09/28/2021

DOI: 10.3390/antiox10101539

PMCID: PMC8532805

PMID: 34679674

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Abstract

BACE1 is a key enzyme facilitating the generation of neurotoxic beta-amyloid (A beta) peptide. However, given that BACE1 has multiple substrates we explored the importance of BACE1 in the maintenance of retinal pigment epithelial (RPE) cell homeostasis under oxidative stress. Inhibition of BACE1 reduced mitochondrial membrane potential, increased mitochondrial fragmentation, and increased cleaved caspase-3 expression in cells under oxidative stress. BACE1 inhibition also resulted in significantly lower levels of mitochondrial fusion proteins OPA1 and MFN1 suggesting a higher rate of mitochondrial fission while increasing the levels of mitophagic proteins Parkin and PINK1 and autophagosome numbers. In contrast, BACE2 had minimal effect on cellular response to oxidative stress. In summary, our results emphasize the importance of BACE1 in augmenting cellular defense against oxidative stress by protecting mitochondrial dynamics.

Biochemistry & Molecular Biology

Chemistry, Medicinal

Food Science & Technology

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

Details

Title: Subtitle: BACE1 Inhibition Increases Susceptibility to Oxidative Stress by Promoting Mitochondrial Damage
Creators: Carolina Francelin - University of Alabama at Birmingham
Sayak K. Mitter - University of Alabama at Birmingham
Qingwen Qian - Indiana University
Sandeep Kumar Barodia - University of Alabama at Birmingham
Colin Ip - Indiana University
Xiaoping Qi - University of Alabama at Birmingham
Hongmei Gu - Indiana University
Judith Quigley - Indiana University
Matthew S. Goldberg - University of Alabama at Birmingham
Maria B. Grant - University of Alabama at Birmingham
Michael E. Boulton - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: Antioxidants, Vol.10(10), p.1539
DOI: 10.3390/antiox10101539
PMID: 34679674
PMCID: PMC8532805
NLM abbreviation: Antioxidants (Basel)
ISSN: 2076-3921
eISSN: 2076-3921
Publisher: Mdpi
Number of pages: 17
Grant note: P30 EY03039 / NEI Core grant R01 NS082565 / NIH NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Research to Prevent Blindness; Research to Prevent Blindness (RPB)
Language: English
Date published: 09/28/2021
Academic Unit: Anatomy and Cell Biology
Record Identifier: 9984420928002771

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