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Should we consider subcellular compartmentalization of metabolites, and if so, how do we measure them?

Wellen, Kathryn E.a,b; Snyder, Nathaniel W.c

Current Opinion in Clinical Nutrition & Metabolic Care: September 2019 - Volume 22 - Issue 5 - p 347–354
doi: 10.1097/MCO.0000000000000580
ASSESSMENT OF NUTRITIONAL AND METABOLIC STATUS: Edited by Dwight E. Matthews and Kristina Norman

Purpose of review To examine the consequences of metabolism compartmentalized at the subcellular level, provide prototypical examples of compartmentalized metabolism, and describe methods to examine compartmentalized metabolism.

Recent findings Progress in metabolomics and isotope tracing has underscored the importance of subcellular compartments of metabolism. The discovery of biological effects of metabolites as bioenergetic intermediates, anabolic building blocks, signaling mediators, and effectors in posttranslation modifications of proteins and nucleic acids have highlighted the role of compartmentalization in determining metabolic fate. Recent advances in both direct and indirect methods to quantify compartmentalized metabolism have improved upon historical approaches. Genetically encoded metabolite sensors, chemical probes, immunoaffinity purification, and compartment-resolved metabolic modeling have all been recently applied to study compartmentalization.

Summary Accurate measurement of metabolites in distinct subcellular compartments is important for understanding and pharmacologically targeting metabolic pathways in diverse disease contexts, including cancer, diabetes, heart failure, obesity, and regulation of the immune system. Direct and indirect approaches to quantify compartmentalized metabolism are advancing rapidly. Yet, major challenges remain in the generalizability, rigor, and interpretation of data from the available methods to quantify compartmentalized metabolism.

aDepartment of Cancer Biology

bAbramson Family Cancer Research Institute, University of Pennsylvania Perelman School of Medicine

cA.J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania, USA

Correspondence to Nathaniel W. Snyder, 3020 Market Street, Suite 560, Philadelphia, PA 19104, USA. E-mail:

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