Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria

Chung Yu Chan, Anthony M. Pedley, Doory Kim, Chenglong Xia, Xiaowei Zhuang, Stephen Benkovic

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)13009-13014
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number51
DOIs
StatePublished - Dec 18 2018

All Science Journal Classification (ASJC) codes

  • General

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