Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons

Catherine M. Drerup, Amy L. Herbert, Kelly Monk, Alex Nechiporuk

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.

Original languageEnglish (US)
Article numbere22234
JournaleLife
Volume6
DOIs
StatePublished - Apr 17 2017

Fingerprint

Mitochondria
Axons
Dyneins
Zebrafish
Dynactin Complex
Health
Phenotype
Defects
Mutation
Networks (circuits)
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons. / Drerup, Catherine M.; Herbert, Amy L.; Monk, Kelly; Nechiporuk, Alex.

In: eLife, Vol. 6, e22234, 17.04.2017.

Research output: Contribution to journalArticle

@article{6a5d8751c11b4fe9a4b1427a3e319d65,
title = "Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons",
abstract = "Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.",
author = "Drerup, {Catherine M.} and Herbert, {Amy L.} and Kelly Monk and Alex Nechiporuk",
year = "2017",
month = "4",
day = "17",
doi = "10.7554/eLife.22234",
language = "English (US)",
volume = "6",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Regulation of mitochondria-dynactin interaction and mitochondrial retrograde transport in axons

AU - Drerup, Catherine M.

AU - Herbert, Amy L.

AU - Monk, Kelly

AU - Nechiporuk, Alex

PY - 2017/4/17

Y1 - 2017/4/17

N2 - Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.

AB - Mitochondrial transport in axons is critical for neural circuit health and function. While several proteins have been found that modulate bidirectional mitochondrial motility, factors that regulate unidirectional mitochondrial transport have been harder to identify. In a genetic screen, we found a zebrafish strain in which mitochondria fail to attach to the dynein retrograde motor. This strain carries a loss-of-function mutation in actr10, a member of the dynein-associated complex dynactin. The abnormal axon morphology and mitochondrial retrograde transport defects observed in actr10 mutants are distinct from dynein and dynactin mutant axonal phenotypes. In addition, Actr10 lacking the dynactin binding domain maintains its ability to bind mitochondria, arguing for a role for Actr10 in dynactin-mitochondria interaction. Finally, genetic interaction studies implicated Drp1 as a partner in Actr10-dependent mitochondrial retrograde transport. Together, this work identifies Actr10 as a factor necessary for dynactin-mitochondria interaction, enhancing our understanding of how mitochondria properly localize in axons.

UR - http://www.scopus.com/inward/record.url?scp=85018916605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018916605&partnerID=8YFLogxK

U2 - 10.7554/eLife.22234

DO - 10.7554/eLife.22234

M3 - Article

VL - 6

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e22234

ER -