Int J Biochem Mol Biol 2011;2(4):347-361
Review Article
Ceramide and mitochondria in ischemic brain injury
Sergei A Novgorodov1, Tatyana I Gudz2
Medicine of Medical University of South Carolina, Charleston, South Carolina, USA; Departments of Neuroscience, Medicine of Medical
University of South Carolina, Charleston, South Carolina, USA
Received November 22, 2011; accepted November 22, 2011; Epub November 25, 2011; Published December 15, 2011
Abstract: Sphingolipids are essential structural components of cellular membranes, playing prominent roles in signal transduction that
governs cell proliferation, differentiation and apoptosis. Ceramides, a family of distinct molecular species characterized by various acyl chains,
are synthesized de novo at the cytosolic side of the endoplasmic reticulum serving as precursors for the biosynthesis of sphingolipids in the
Golgi. Recently, mitochondria emerged as an important intracellular compartment of sphingolipid metabolism. Thus, several
sphingolipid-metabolizing enzymes were found to be associated with mitochondria, including neutral ceramidase, novel neutral
sphingomyelinase, and (dihydro) ceramide synthase, an important ceramide-generating enzyme in de novo ceramide synthesis and recycling
pathway. Mitochondrial dysfunction appears to be essential in tissue damage after brain ischemia/reperfusion (IR). Mitochondria are known to
be involved in both the necrosis and apoptosis detected in animal models of ischemic stroke, and treatments that ameliorate tissue infarction
were associated with better recovery of mitochondrial function. Although mitochondrial injury in stroke has been extensively studied and key
mitochondrial functions affected by IR are mainly characterized, the nature of the molecule that causes loss of mitochondrial integrity and
function remains obscure. Emerging data indicate a deregulation of ceramide metabolism in mitochondria damaged by IR suggesting that
ceramides could play critical roles in cerebral IR-induced mitochondrial damage. This review will examine the experimental evidence
supporting the key role of ceramides in mitochondrial dysfunction in cerebral IR and highlight potential targets for development of novel
therapeutic approaches for stroke treatment.
(IJBMB1111001).
Keywords: Sphingolipid, ceramide, ceramide synthase, neutral ceramidase, mitochondria, stroke
Full Text PDF
Address all correspondence to:
Dr. Tatyana I Gudz
Department of Neurosciences
Medical University of South Carolina
114 Doughty St. Charleston, SC 29425, USA.
Tel: 843 792-6439; Fax: 843 876-5099
E-Mail: gudz@musc.edu
Review Article
Ceramide and mitochondria in ischemic brain injury
Sergei A Novgorodov1, Tatyana I Gudz2
Medicine of Medical University of South Carolina, Charleston, South Carolina, USA; Departments of Neuroscience, Medicine of Medical
University of South Carolina, Charleston, South Carolina, USA
Received November 22, 2011; accepted November 22, 2011; Epub November 25, 2011; Published December 15, 2011
Abstract: Sphingolipids are essential structural components of cellular membranes, playing prominent roles in signal transduction that
governs cell proliferation, differentiation and apoptosis. Ceramides, a family of distinct molecular species characterized by various acyl chains,
are synthesized de novo at the cytosolic side of the endoplasmic reticulum serving as precursors for the biosynthesis of sphingolipids in the
Golgi. Recently, mitochondria emerged as an important intracellular compartment of sphingolipid metabolism. Thus, several
sphingolipid-metabolizing enzymes were found to be associated with mitochondria, including neutral ceramidase, novel neutral
sphingomyelinase, and (dihydro) ceramide synthase, an important ceramide-generating enzyme in de novo ceramide synthesis and recycling
pathway. Mitochondrial dysfunction appears to be essential in tissue damage after brain ischemia/reperfusion (IR). Mitochondria are known to
be involved in both the necrosis and apoptosis detected in animal models of ischemic stroke, and treatments that ameliorate tissue infarction
were associated with better recovery of mitochondrial function. Although mitochondrial injury in stroke has been extensively studied and key
mitochondrial functions affected by IR are mainly characterized, the nature of the molecule that causes loss of mitochondrial integrity and
function remains obscure. Emerging data indicate a deregulation of ceramide metabolism in mitochondria damaged by IR suggesting that
ceramides could play critical roles in cerebral IR-induced mitochondrial damage. This review will examine the experimental evidence
supporting the key role of ceramides in mitochondrial dysfunction in cerebral IR and highlight potential targets for development of novel
therapeutic approaches for stroke treatment.
(IJBMB1111001).
Keywords: Sphingolipid, ceramide, ceramide synthase, neutral ceramidase, mitochondria, stroke
Full Text PDF
Address all correspondence to:
Dr. Tatyana I Gudz
Department of Neurosciences
Medical University of South Carolina
114 Doughty St. Charleston, SC 29425, USA.
Tel: 843 792-6439; Fax: 843 876-5099
E-Mail: gudz@musc.edu
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