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TitleFMRP regulates MFF translation to locally direct mitochondrial fission in neurons.
Journal, issue, pagesNat Cell Biol, Vol. 26, Issue 12, Page 2061-2074, Year 2024
Publish dateNov 15, 2024
AuthorsAdam R Fenton / Ruchao Peng / Charles Bond / Siewert Hugelier / Melike Lakadamyali / Yi-Wei Chang / Erika L F Holzbaur / Thomas A Jongens /
PubMed AbstractFragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile X syndrome. FMRP dysfunction disrupts mitochondrial health in neurons, but it is ...Fragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile X syndrome. FMRP dysfunction disrupts mitochondrial health in neurons, but it is unclear how FMRP supports mitochondrial homoeostasis. Here we demonstrate that FMRP granules are recruited to the mitochondrial midzone, where they mark mitochondrial fission sites in axons and dendrites. Endolysosomal vesicles contribute to FMRP granule positioning around mitochondria and facilitate FMRP-associated fission via Rab7 GTP hydrolysis. Cryo-electron tomography and real-time translation imaging reveal that mitochondria-associated FMRP granules are ribosome-rich structures that serve as sites of local protein synthesis. Specifically, FMRP promotes local translation of mitochondrial fission factor (MFF), selectively enabling replicative fission at the mitochondrial midzone. Disrupting FMRP function dysregulates mitochondria-associated MFF translation and perturbs fission dynamics, resulting in increased peripheral fission and an irregular distribution of mitochondrial nucleoids. Thus, FMRP regulates local translation of MFF in neurons, enabling precise control of mitochondrial fission.
External linksNat Cell Biol / PubMed:39548330 / PubMed Central
MethodsEM (tomography)
Structure data

EMDB-47150: Mitochondrial fission site in neurons at the constriction stage
Method: EM (tomography)

EMDB-47151: Mitochondrial fission site in neurons at the post fission state 1
Method: EM (tomography)

EMDB-47152: Mitochondrial fission site in neurons at the post fission state 2
Method: EM (tomography)

Source
  • Rattus norvegicus (Norway rat)

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