Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Precisely control mitochondria with light to manipulate cell fate decision

Patrick Ernst, Ningning Xu, Jing Qu, Herbert Chen, Matthew S. Goldberg, Victor Darley-Usmar, Jianyi J. Zhang, Brian O’Rourke, Xiaoguang Liu, Lufang Zhou
doi: https://doi.org/10.1101/469668
Patrick Ernst
1Departments of Biomedical Engineering University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
2Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ningning Xu
1Departments of Biomedical Engineering University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing Qu
2Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Herbert Chen
3Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew S. Goldberg
4Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Victor Darley-Usmar
5Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianyi J. Zhang
1Departments of Biomedical Engineering University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian O’Rourke
6Division of Cardiology, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, USA, 21205
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoguang Liu
1Departments of Biomedical Engineering University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lufang Zhou
1Departments of Biomedical Engineering University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
2Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA, 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: lfzhou@uab.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Mitochondrial dysfunction has been implicated in many pathological conditions and diseases. The normal functioning of mitochondria relies on maintaining the inner mitochondrial membrane (IMM) potential (a.k.a. ΔΨm) that is essential for ATP synthesis, Ca2+ homeostasis, redox balance and regulation of other key signaling pathways such as mitophagy and apoptosis. However, the detailed mechanisms by which ΔΨm regulates cellular function remain incompletely understood, partially due to difficulty of manipulating ΔΨm with spatiotemporal resolution, reversibility, or cell type specificity. To address this need, we have developed a next-generation optogenetic-based technique for controllable mitochondrial depolarization with light. We demonstrate successful targeting of the heterologous Channelrhodopsin-2 (ChR2) fusion protein to the IMM and formation of functional cationic channels capable of light-induced selective ΔΨm depolarization and mitochondrial autophagy. Importantly, we for the first time show that optogenetic-mediated mitochondrial depolarization can be well-controlled to differentially influence the fate of cells expressing mitochondrial ChR2: while sustained moderate light illumination induces substantial apoptotic cell death, transient mild light illumination elicits cytoprotection via mitochondrial preconditioning. Finally, we show that Parkin overexpression exacerbates, instead of ameliorating, mitochondrial depolarization-mediated cell death in HeLa cells. In summary, we provide evidence that the described mitochondrial-targeted optogenetics may have a broad application for studying the role of mitochondria in regulating cell function and fate decision.

Footnotes

  • updating figures

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted May 29, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Precisely control mitochondria with light to manipulate cell fate decision
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Precisely control mitochondria with light to manipulate cell fate decision
Patrick Ernst, Ningning Xu, Jing Qu, Herbert Chen, Matthew S. Goldberg, Victor Darley-Usmar, Jianyi J. Zhang, Brian O’Rourke, Xiaoguang Liu, Lufang Zhou
bioRxiv 469668; doi: https://doi.org/10.1101/469668
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Precisely control mitochondria with light to manipulate cell fate decision
Patrick Ernst, Ningning Xu, Jing Qu, Herbert Chen, Matthew S. Goldberg, Victor Darley-Usmar, Jianyi J. Zhang, Brian O’Rourke, Xiaoguang Liu, Lufang Zhou
bioRxiv 469668; doi: https://doi.org/10.1101/469668

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
  • Biophysics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4383)
  • Biochemistry (9599)
  • Bioengineering (7094)
  • Bioinformatics (24865)
  • Biophysics (12616)
  • Cancer Biology (9958)
  • Cell Biology (14355)
  • Clinical Trials (138)
  • Developmental Biology (7951)
  • Ecology (12107)
  • Epidemiology (2067)
  • Evolutionary Biology (15989)
  • Genetics (10926)
  • Genomics (14743)
  • Immunology (9870)
  • Microbiology (23677)
  • Molecular Biology (9485)
  • Neuroscience (50872)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2683)
  • Physiology (4016)
  • Plant Biology (8657)
  • Scientific Communication and Education (1509)
  • Synthetic Biology (2397)
  • Systems Biology (6436)
  • Zoology (1346)