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research-article

Compartmentalization of Bioenergetic Substrate Delivery in Intact Cells

[+] Author and Article Information
David Eckmann

Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
eckmanndm@uphs.upenn.edu

Abhay Ranganathan

Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
abhay.ranganathan@uphs.upenn.edu

Shawn Owiredu

Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
shawn.owiredu@uphs.upenn.edu

David Jang

Department of Emergency Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
david.jang@uphs.upenn.edu

1Corresponding author.

ASME doi:10.1115/1.4042186 History: Received August 28, 2018; Revised November 22, 2018

Abstract

The intracellular production and transport of energetic substrate adenosine triphosphate (ATP) produced by mitochondria is dependent on multiple factors. These include local metabolic demand, mitochondrial motility and intracellular location, mitochondrial intermembrane potential, bioenergy substrate diffusion within the cell cytosol and energy transport to the cell nucleus, which itself does not contain any mitochondria. Herein we demonstrate via cell-based experiment and scaling argument that intracellular bioenergy transport is readily compartmentalized into perinuclear and peripheral regions of the cell. We draw on direct fluorescence-based measurement of quantum dot tracking, high-resolution respirometry, mitochondrial dynamics and intermembrane potential to assess intracellular quantum dot diffusion to define the intracellular milieu for small molecule transport, and chemical perturbations which challenge cells by altering bioenergetics states. We identify a heterogeneous environment for intracellular bioenergy transport, with a dominant feature being present: the intracellular bioenergy distribution in response to pharmacologically-induced cell challenge is determined to be preservation of perinuclear mitochondrial ATP-linked respiration in order to preserve, maintain or otherwise support bioenergy delivery to meet the metabolic requirements of the cell nucleus whereas there is a decrement in bioenergetic capacity in the cell periphery. This dynamic effect of motile intracellular bioenergy production yields efficient transport of ATP in the maintenance of cellular health.

Copyright (c) 2018 by ASME
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