Abstract
One can utilize light illumination to stimulate mitochondrial reactive oxygen species production through the use of mitochondria-specific photosensitizers. By proper tuning of the light dosage, the methodology permits probing of a multitude of mitochondrial damage responses, including mitophagy. This light-controllable trick offers unique opportunities for the investigation of mitophagy—one can spatiotemporally define mitochondrial damage, alter the number of impaired mitochondria, as well as modulate the severity of the mitochondrial injury. This light-activated mitophagy can be adapted not only to single-cell imaging techniques but also to cell population-based biochemical assays.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12(1):9–14
Narendra D, Tanaka A, Suen DF et al (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183(5):795–803
Lazarou M, Narendra DP, Jin SM et al (2013) PINK1 drives Parkin self-association and HECT-like E3 activity upstream of mitochondrial binding. J Cell Biol 200(2):163–172
Lazarou M, Sliter DA, Kane LA et al (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524(7565):309–314
Padman BS, Bach M, Lucarelli G et al (2013) The protonophore CCCP interferes with lysosomal degradation of autophagic cargo in yeast and mammalian cells. Autophagy 9(11):1862–1875
Hsieh CW, Chu CH, Lee HM et al (2015) Triggering mitophagy with far-red fluorescent photosensitizers. Sci Rep 5:10376
Yang JY, Yang WY (2011) Spatiotemporally controlled initiation of Parkin-mediated mitophagy within single cells. Autophagy 7(10):1230–1238
Wong YC, Holzbaur EL (2014) Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A 111(42):E4439–E4448
Ashrafi G, Schlehe JS, LaVoie MJ et al (2014) Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin. J Cell Biol 206(5):655–670
Wang Y, Nartiss Y, Steipe B et al (2012) ROS-induced mitochondrial depolarization initiates PARK2/PARKIN-dependent mitochondrial degradation by autophagy. Autophagy 8(10):1462–1476
Choubey V, Safiulina D, Vaarmann A et al (2011) Mutant A53T alpha-synuclein induces neuronal death by increasing mitochondrial autophagy. J Biol Chem 286(12):10814–10824
Yang JY, Yang WY (2013) Bit-by-bit autophagic removal of parkin-labelled mitochondria. Nat Commun 4:2428
Wojtovich AP, Foster TH (2014) Optogenetic control of ROS production. Redox Biol 2:368–376
Bulina ME, Chudakov DM, Britanova OV et al (2006) A genetically encoded photosensitizer. Nat Biotechnol 24(1):95–99
Takemoto K, Matsuda T, Sakai N et al (2013) SuperNova, a monomeric photosensitizing fluorescent protein for chromophore-assisted light inactivation. Sci Rep 3:2629
Sarkisyan KS, Zlobovskaya OA, Gorbachev DA et al (2015) KillerOrange, a genetically encoded photosensitizer activated by blue and green light. PLoS One 10(12):e0145287
Shu X, Lev-Ram V, Deerinck TJ et al (2011) A genetically encoded tag for correlated light and electron microscopy of intact cells, tissues, and organisms. PLoS Biol 9(4):e1001041
Westberg M, Holmegaard L, Pimenta FM et al (2015) Rational design of an efficient, genetically encodable, protein-encased singlet oxygen photosensitizer. J Am Chem Soc 137(4):1632–1642
He J, Wang Y, Missinato MA et al (2016) A genetically targetable near-infrared photosensitizer. Nat Methods 13(3):263–268
Acknowledgments
This work was supported by the MOST 104-2628-B-001-001-MY4 research grant from the Ministry of Science and Technology in Taiwan.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Hsieh, CW., Yang, W.Y. (2019). Triggering Mitophagy with Photosensitizers. In: Ktistakis, N., Florey, O. (eds) Autophagy. Methods in Molecular Biology, vol 1880. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8873-0_40
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8873-0_40
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8872-3
Online ISBN: 978-1-4939-8873-0
eBook Packages: Springer Protocols