Báo cáo y học: Deficient mitochondrial biogenesis in critical illness: cause, effect, or epiphenomeno

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Deficient mitochondrial biogenesis in critical illness: cause, effect, or epiphenomenon?
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Báo cáo y học: "Deficient mitochondrial biogenesis in critical illness: cause, effect, or epiphenomeno" Available online http://ccforum.com/content/11/4/158CommentaryDeficient mitochondrial biogenesis in critical illness:cause, effect, or epiphenomenon?Richard J Levy1 and Clifford S Deutschman21Maria Fareri Children’s Hospital of Westchester Medical Center, New York Medical College, Valhalla, New York, USA2Department of Anesthesiology and Critical Care and the Stavropoulos Sepsis Research Program, University of Pennsylvania School of Medicine,Philadelphia, Pennsylvania, USACorresponding author: Clifford S Deutschman, deutschcl@uphs.upenn.eduPublished: 24 August 2007 Critical Care 2007, 11:158 (doi:10.1186/cc6098)This article is online at http://ccforum.com/content/11/4/158© 2007 BioMed Central LtdSee related research by Côté et al., http://ccforum.com/content/11/4/R88Abstract conclude that loss or failed synthesis of mtDNA is a unifying cause of sepsis-induced mitochondrial dysfunction and thatRecent studies indicate that mitochondrial dysfunction plays a role clinicians could use mtDNA copy number to predict mortalityin the pathogenesis of a number of disease states. The importance during critical illness. This requires a more detailedof these organelles in shock and multiple organ dysfunction is ofparticular interest to those caring for the critically ill. Mitochondria examination of mtDNA heterogeneity and mitochondrialhave their own unique DNA (mtDNA) that encodes 13 essential regeneration.subunits of electron transport chain enzymes, two ribosomal RNAsand 22 transfer RNAs. Importantly, mtDNA is especially sus- Each mitochondrion has 2-10 copies of its own circularceptible to deletions, rearrangements and mutations because it is genome. These encode for 13 essential subunits of electronnot bound by histones and lacks the extensive repair machinery transport chain enzymes, two ribosomal RNAs and 22present in the nucleus. The study by Côté et al. in this issue ofCritical Care examines changes in mtDNA in critically ill patients. transfer RNAs [7]. The structural subunits of the electronThe results support further investigation into the role of mtDNA in transport complexes and other mitochondrial proteins arisethe critically ill. from nuclear genes [8]. Thus, expression of the genes encoding mitochondrial enzyme complexes is under dualThe role of mitochondria in systemic disease has been under- control. mtDNA is particularly prone to deletions, rearrange-appreciated, and in this issue of Critical Care, Côté et al. [1] ments and mutations caused by oxidative stress because it isexamine changes in mitochondrial DNA (mtDNA) in critically unbound by histones and because these organelles lack theill patients. However, recent evidence has demonstrated extensive repair systems seen in the nucleus [9]. Therefore,impaired oxidative phosphorylation and defective mitochon- reactive oxygen species produced during oxidativedrial homeostasis in a number of disorders [2,3]. Although phosphorylation in a variety of disease states can damagethe concept of mitochondrial dysfunction and bioenergetic mtDNA and mitochondrial proteins. This would lead tofailure during sepsis and shock is not new, recent decreased ATP production and enhanced programmed cellexperimental approaches have yielded novel and interesting death [7].findings [4-6]. These have led us and others to proposeintriguing hypotheses regarding the pathogenesis of acquired Heteroplasmy describes the coexistence of both mutantmitochondrial dysfunction in a variety of disease states. mtDNA and wild-type, non-mutant mtDNA within the same cell [8]. If the mitochondrial genome drift results in a signifi-In this issue, Côté et al. examine changes in mtDNA in cant ...