Emerging role of AMP-activated protein kinase in coupling... : Current Opinion in Nephrology and Hypertension (original) (raw)

Molecular cell biology and physiology of solute transport

Emerging role of AMP-activated protein kinase in coupling membrane transport to cellular metabolism

Renal-Electrolyte Division, Department of Medicine and Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA

Correspondence to Kenneth R. Hallows, MD, PhD, Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, S976 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA Tel: +1 412 648 9580; fax: +1 412 383 8956; e-mail: [email protected]

Abstract

Purpose of review

It has long been recognized that the coupling of membrane transport to underlying cellular metabolic status is critical because transport processes consume a large portion of total cellular energy. Recently, the finely tuned metabolic sensor AMP-activated protein kinase (AMPK) has emerged as a membrane transport regulator, which may permit sensitive transport-metabolism crosstalk. This review will discuss how AMPK may play an important role in the regulation of ion and solute transport across the plasma membrane under both physiological and pathological conditions in epithelia and other tissues.

Recent findings

Recent studies have found that AMPK, which becomes activated during cellular metabolic stress, promotes the cellular uptake of fuel sources such as glucose and fatty acids to promote ATP generation and inhibits ion-transport proteins such as the cystic fibrosis transmembrane conductance regulator Cl− channel and the epithelial Na+ channel, thereby limiting the dissipation of transmembrane ion gradients. An understanding of the underlying cellular and molecular mechanisms for AMPK-dependent regulation of transport proteins is beginning to emerge.

Summary

As earlier studies have focused on the role of nucleotides such as ATP in regulating transport-protein activities, the regulation of membrane transport by AMPK represents a novel and more-sensitive mechanism for the coupling of membrane transport to cellular metabolic status. Identifying new membrane-transport targets of AMPK and elucidating the mechanisms involved in their AMPK-dependent regulation are fruitful areas for new investigation that should yield valuable insights into the pathophysiology of hypoxic and ischemic tissue injury.