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(Circulation Research. 2001;89:108.)
© 2001 American Heart Association, Inc.

Editorial

The Cytoplasm

No Longer a Well-Mixed Bag

James N. Weiss, Paavo Korge

From the Cardiovascular Research Laboratory and the Departments of Medicine (Cardiology) and Physiology, University of California Los Angeles School of Medicine, Los Angeles, Calif.

Correspondence to James N. Weiss, MD, 3645 MRL Building, UCLA School of Medicine, Los Angeles, CA 90095-1760. E-mail jweiss@mednet.ucla.edu

Key Words: metabolism • bioenergetics • compartmentalization • sarcoplasmic reticulum Ca²⁺ ATPase • high-energy phosphates

Until the last decade or so, many intracellular signaling pathways were viewed as processes in which second messengers diffused uniformly through a well-mixed milieu of the cell’s cytoplasm to reach their targets. Although it was recognized that the cell’s interior was compartmentalized, this compartmentalization was believed to be largely defined by internal membranes, such as the nuclear envelope, endoplasmic reticulum (ER), sarcoplasmic reticulum (SR), and mitochondria. But like the joke about the person who has lost his keys in the dark but looks for them under the street lamp because the light is better, this view of the cytoplasm as a well-mixed milieu was less of a proven fact than a simplifying assumption. Over the last decade, advances in subcellular imaging have dramatically upset this view, so that now a high degree of compartmentalization of signaling pathways within the cytoplasm is considered the norm rather than the exception. It is now clear that the cytoplasm has a highly organized cytoskeleton and sophisticated molecular trafficking mechanisms that direct and tether proteins into macroaggregates at specific locations to facilitate localized signaling. The cytoplasm is now viewed as a system of microdomains with restricted diffusion (eg, hierarchical Ca²⁺ signaling) and direct channeling of substrates to enzymes (eg, protein kinases/phosphatases cascades).

In the field of metabolism, subcellular compartmentation of energy production has been a well-accepted fact ever since mitochondria were identified as the engines driving aerobic high-energy phosphate production. In addition, glycolytic enzymes complexes are well-known to be associated with specific intracellular structures, such . . . [Full Text of this Article]

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