Cell Reports
Volume 21, Issue 6, 7 November 2017, Pages 1667-1680
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Article
ROS Control Mitochondrial Motility through p38 and the Motor Adaptor Miro/Trak

https://doi.org/10.1016/j.celrep.2017.10.060Get rights and content
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Highlights

  • ROS induce a reversible decrease in mitochondrial motility

  • ROS-induced motility decrease is triggered independently of [Ca2+]c

  • ROS-induced motility decrease does not require PTP opening or ΔΨm dissipation

  • p38α and the motor adaptor complex are required for ROS control of motility

Summary

Mitochondrial distribution and motility are recognized as central to many cellular functions, but their regulation by signaling mechanisms remains to be elucidated. Here, we report that reactive oxygen species (ROS), either derived from an extracellular source or intracellularly generated, control mitochondrial distribution and function by dose-dependently, specifically, and reversibly decreasing mitochondrial motility in both rat hippocampal primary cultured neurons and cell lines. ROS decrease motility independently of cytoplasmic [Ca2+], mitochondrial membrane potential, or permeability transition pore opening, known effectors of oxidative stress. However, multiple lines of genetic and pharmacological evidence support that a ROS-activated mitogen-activated protein kinase (MAPK), p38α, is required for the motility inhibition. Furthermore, anchoring mitochondria directly to kinesins without involvement of the physiological adaptors between the organelles and the motor protein prevents the H2O2-induced decrease in mitochondrial motility. Thus, ROS engage p38α and the motor adaptor complex to exert changes in mitochondrial motility, which likely has both physiological and pathophysiological relevance.

Keywords

reactive oxygen species
mitochondria
movement
calcium
permeability transition
p38
Miro
TRAK

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These authors contributed equally

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