Mitochondria play a central role in nonischemic cardiomyocyte necrosis: Common to acute and chronic stressor states

M. Usman Khan, Yaser Cheema, Atta U. Shahbaz, Robert A. Ahokas, Yao Sun, Ivan Gerling, Syamal Bhattacharya, Karl Weber

Research output: Contribution to journalReview article

18 Citations (Scopus)

Abstract

The survival of cardiomyocytes must be ensured as the myocardium adjusts to a myriad of competing physiological and pathophysiological demands. A significant loss of these contractile cells, together with their replacement by stiff fibrillar collagen in the form of fibrous tissue accounts for a transition from a usually efficient muscular pump into one that is failing. Cellular and subcellular mechanisms involved in the pathogenic origins of cardiomyocyte cell death have long been of interest. This includes programmed molecular pathways to either necrosis or apoptosis, which are initiated from ischemic or nonischemic origins. Herein, we focus on the central role played by a mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis, which is common to acute and chronic stressor states. We begin by building upon the hypothesis advanced by Albrecht Fleckenstein and coworkers some 40 years ago based on the importance of calcitropic hormone-mediated intracellular Ca 2+ overloading, which predominantly involves subsarcolemmal mitochondria and is the signal to pathway activation. Other pathway components, which came to be recognized in subsequent years, include the induction of oxidative stress and opening of the mitochondrial inner membrane permeability transition pore. The ensuing loss of cardiomyocytes and consequent replacement fibrosis, or scarring, represents a disease of adaptation and a classic example of when homeostasis begets dyshomeostasis.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalPflugers Archiv European Journal of Physiology
Volume464
Issue number1
DOIs
StatePublished - Jul 1 2012

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Mitochondria
Cardiac Myocytes
Necrosis
Fibrillar Collagens
Oxidative stress
Cell death
Transducers
Chemical activation
Pumps
Hormones
Tissue
Apoptosis
Membranes
Mitochondrial Membranes
Cicatrix
Permeability
Signal Transduction
Myocardium
Oxidative Stress
Homeostasis

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

Cite this

Mitochondria play a central role in nonischemic cardiomyocyte necrosis : Common to acute and chronic stressor states. / Khan, M. Usman; Cheema, Yaser; Shahbaz, Atta U.; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan; Bhattacharya, Syamal; Weber, Karl.

In: Pflugers Archiv European Journal of Physiology, Vol. 464, No. 1, 01.07.2012, p. 123-131.

Research output: Contribution to journalReview article

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