Journal article
Spatial colocalization and functional link of purinosomes with mitochondria
Science (American Association for the Advancement of Science), Vol.351(6274), pp.733-737
02/12/2016
DOI: 10.1126/science.aac6054
PMCID: PMC4881839
PMID: 26912862
Abstract
Purine biosynthetic enzymes organize into dynamic cellular bodies called purinosomes. Little is known about the spatiotemporal control of these structures. Using super-resolution microscopy, we demonstrated that purinosomes colocalized with mitochondria, and these results were supported by isolation of purinosome enzymes with mitochondria. Moreover, the number of purinosome-containing cells responded to dysregulation of mitochondrial function and metabolism. To explore the role of intracellular signaling, we performed a kinome screen using a label-free assay and found that mechanistic target of rapamycin (mTOR) influenced purinosome assembly. mTOR inhibition reduced purinosome-mitochondria colocalization and suppressed purinosome formation stimulated by mitochondria dysregulation. Collectively, our data suggest an mTOR-mediated link between purinosomes and mitochondria, and a general means by which mTOR regulates nucleotide metabolism by spatiotemporal control over protein association.
Details
- Title: Subtitle
- Spatial colocalization and functional link of purinosomes with mitochondria
- Creators
- Jarrod B. French - Stony Brook UniversitySara A. Jones - Harvard UniversityHuayun Deng - CorningAnthony M. Pedley - Pennsylvania State UniversityDoory Kim - Harvard UniversityChung Yu Chan - Pennsylvania State UniversityHaibei Hu - CorningRaymond J. Pugh - Pennsylvania State UniversityHong Zhao - Pennsylvania State UniversityYouxin Zhang - Harvard UniversityTony Jun Huang - Pennsylvania State UniversityYe Fang - BioChem TechnologyXiaowei Zhuang - Harvard UniversityStephen J. Benkovic - Pennsylvania State University
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.351(6274), pp.733-737
- DOI
- 10.1126/science.aac6054
- PMID
- 26912862
- PMCID
- PMC4881839
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 7
- Grant note
- R01GM024129 / 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) R33EB019785 / NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) NIH GM024129; 1R33EB019785-01 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Howard Hughes Medical Institute Pennsylvania Department of Health Tobacco Settlement Funds Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR)
- Language
- English
- Date published
- 02/12/2016
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984771652302771
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