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- Title
All-optical spatiotemporal mapping of ROS dynamics across mitochondrial microdomains in situ.
- Authors
Koren, Shon A.; Ahmed Selim, Nada; De la Rosa, Lizbeth; Horn, Jacob; Farooqi, M. Arsalan; Wei, Alicia Y.; Müller-Eigner, Annika; Emerson, Jacen; Johnson, Gail V. W.; Wojtovich, Andrew P.
- Abstract
Hydrogen peroxide (H2O2) functions as a second messenger to signal metabolic distress through highly compartmentalized production in mitochondria. The dynamics of reactive oxygen species (ROS) generation and diffusion between mitochondrial compartments and into the cytosol govern oxidative stress responses and pathology, though these processes remain poorly understood. Here, we couple the H2O2 biosensor, HyPer7, with optogenetic stimulation of the ROS-generating protein KillerRed targeted into multiple mitochondrial microdomains. Single mitochondrial photogeneration of H2O2 demonstrates the spatiotemporal dynamics of ROS diffusion and transient hyperfusion of mitochondria due to ROS. This transient hyperfusion phenotype required mitochondrial fusion but not fission machinery. Measurement of microdomain-specific H2O2 diffusion kinetics reveals directionally selective diffusion through mitochondrial microdomains. All-optical generation and detection of physiologically-relevant concentrations of H2O2 between mitochondrial compartments provide a map of mitochondrial H2O2 diffusion dynamics in situ as a framework to understand the role of ROS in health and disease. How ROS diffuse and are cleared between mitochondrial compartments governs oxidative stress and cell signaling. Here, authors map the kinetics of ROS dynamics using optogenetics and discover acute ROS transiently elongates mitochondria.
- Subjects
MITOCHONDRIA; DIFFUSION kinetics; REACTIVE oxygen species; HYDROGEN peroxide; CELL communication; OXYGEN consumption; CELL fusion
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-41682-z