TY - JOUR
T1 - Preserving Mitochondrial Structure and Motility Promotes Recovery of White Matter After Ischemia
AU - Bastian, Chinthasagar
AU - Day, Jerica
AU - Politano, Stephen
AU - Quinn, John
AU - Brunet, Sylvain
AU - Baltan, Selva
N1 - Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Stroke significantly affects white matter in the brain by impairing axon function, which results in clinical deficits. Axonal mitochondria are highly dynamic and are transported via microtubules in the anterograde or retrograde direction, depending upon axonal energy demands. Recently, we reported that mitochondrial division inhibitor 1 (Mdivi-1) promotes axon function recovery by preventing mitochondrial fission only when applied during ischemia. Application of Mdivi-1 after injury failed to protect axon function. Interestingly, L-NIO, which is a NOS3 inhibitor, confers post-ischemic protection to axon function by attenuating mitochondrial fission and preserving mitochondrial motility via conserving levels of the microtubular adaptor protein Miro-2. We propose that preventing mitochondrial fission protects axon function during injury, but that restoration of mitochondrial motility is more important to promote axon function recovery after injury. Thus, Miro-2 may be a therapeutic molecular target for recovery following a stroke.
AB - Stroke significantly affects white matter in the brain by impairing axon function, which results in clinical deficits. Axonal mitochondria are highly dynamic and are transported via microtubules in the anterograde or retrograde direction, depending upon axonal energy demands. Recently, we reported that mitochondrial division inhibitor 1 (Mdivi-1) promotes axon function recovery by preventing mitochondrial fission only when applied during ischemia. Application of Mdivi-1 after injury failed to protect axon function. Interestingly, L-NIO, which is a NOS3 inhibitor, confers post-ischemic protection to axon function by attenuating mitochondrial fission and preserving mitochondrial motility via conserving levels of the microtubular adaptor protein Miro-2. We propose that preventing mitochondrial fission protects axon function during injury, but that restoration of mitochondrial motility is more important to promote axon function recovery after injury. Thus, Miro-2 may be a therapeutic molecular target for recovery following a stroke.
KW - Ischemia
KW - Miro-2
KW - Mitochondria
KW - Mitochondrial dynamics
KW - NOS3
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=85066505206&partnerID=8YFLogxK
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U2 - 10.1007/s12017-019-08550-w
DO - 10.1007/s12017-019-08550-w
M3 - Article
C2 - 31152363
AN - SCOPUS:85066505206
SN - 1535-1084
VL - 21
SP - 484
EP - 492
JO - NeuroMolecular Medicine
JF - NeuroMolecular Medicine
IS - 4
ER -