Journal article
Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria
Proceedings of the National Academy of Sciences - PNAS, Vol.115(51), pp.13009-13014
12/18/2018
DOI: 10.1073/pnas.1814042115
PMCID: PMC6304990
PMID: 30509995
Abstract
To meet their purine demand, cells activate the de novo purine biosynthetic pathway and transiently cluster the pathway enzymes into metabolons called purinosomes. Recently, we have shown that purinosomes were spatially colocalized with mitochondria and microtubules, yet it remained unclear as to what drives these associations and whether a relationship between them exist. Here, we employed superresolution imaging methods to describe purinosome transit in the context of subcellular localization. Time-resolved imaging of purinosomes showed that these assemblies exhibit directed motion as they move along a microtubule toward mitochondria, where upon colocalization, a change in purinosome motion was observed. A majority of purinosomes colocalized with mitochondria were also deemed colocalized with microtubules. Nocodazole-dependent microtubule depolymerization resulted in a loss in the purinosome-mitochondria colocalization, suggesting that the association of purinosomes with mitochondria is facilitated by microtubule-directed transport, and thereby supporting our notion of an interdependency between these subcellular components in maximizing purine production through the de novo purine biosynthetic pathway.
Details
- Title: Subtitle
- Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria
- Creators
- Chung Yu Chan - Pennsylvania State UniversityAnthony M. Pedley - Pennsylvania State UniversityDoory Kim - Harvard UniversityChenglong Xia - Harvard UniversityXiaowei Zhuang - Harvard UniversityStephen J. Benkovic - Pennsylvania State University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.115(51), pp.13009-13014
- DOI
- 10.1073/pnas.1814042115
- PMID
- 30509995
- PMCID
- PMC6304990
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- GM024129 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Howard Hughes Medical Institute R35GM122487 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 12/18/2018
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984771648502771
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