Talk:Lemieux 2011 Int J Biochem Cell Biol

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Human heart failure: mtDNA versus CS and PGC-1a pathway

We have recently published 2 articles which are focused on mtDNA changes in heart failure. In our first publication, we reported disproportional decrease of mtDNA content compared to citrate synthase activity in end stage human heart failure. In our more recent publication, we showed that mtDNA is decreased in the stage of cardiac hypertrophy without significant changes in citrate synthase activity in humans. The references are listed below. Regards

Georgios (9 November 2011)

Georgios Karamanlidis, PhD Acting Instructor Mitochondrial and Metabolism Center University of Washington 815 Mercer Street Room N130 Mailbox# 358057 Seattle, WA 98109 Tel: (206) 543 8207 email: georgios@u.washington.edu

  • Karamanlidis G, Bautista-Hernandez V, Fynn-Thompson F, Del Nido P, Tian R (2011) Impaired mitochondrial biogenesis precedes heart failure in right ventricular hypertrophy in congenital heart disease. Circ. Heart Fail. Aug 2011. In press.
  • Karamanlidis G, Nascimben L, Couper GS, Shekar PS, del Monte F, Tian R (2010) Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ. Res. 106: 1541-1548.

Dear Georgios: Thank you for posting the two publications on heart failure and mtDNA versus CS activity. Your findings are of interest in relation to Lemieux 2011 IJBCB. Best regards Erich (10 November 2011)


Dear Erich Thanks a lot for your post. This is an interesting paper to us. In our study unfortunately we were unable to obtain fresh donor samples so we could not assess mitochondrial respiratory capacity. But putting together your paper with ours it connects and complement each other nicely. I wondered whether you looked at the PGC-1a pathway? We see down-regulation of the PGC-1a pathway in a mouse model of heart failure but not in humans. Thanks Georgios (10 November 2011)

From the anonymous IJBCB referee's comments

  • Reviewer #1: "The manuscript by Lemieux and colleagues offers interesting insight into the bioenergetics of early phases of heart failure."
  • Reviewer #2: "This is a beautifully written work, replete with well-designed experiments and, within the space limitations, a nice review of the pertinent literature. The demonstration of impaired mitochondrial fatty acid oxidation in early stages of human failure is very important, as is the demonstration of defects in the phosphorylation system and Complex I-linked respiration."
  • Reviewer #3: "The manuscript belongs literally to the symphony of bioenergetics and have mastered on a maximum thorough and detailed level a priority study of human heart disease bioenergetics in an intermediate state of heart disease, which was done only scarcely in medical sciences and for this orthodox approach this work deserves a high attention. It elegantly describes detailed oxidative phosphorylation parameters in heart disease compared to the control human heart. Using high-resolution respirometry of permeabilized human heart muscle fibres authors progressively describe distinct aspect of measured data in logical steps to present important differences of diminished mitochondrial function during heart failure. Using elegant protocols developed for years, authors distinguish between phosphorylating (OXPHOS) and non-phosphorylating (ETS) conditions with both complex I and II input using physiological substrates of glucose and lipid oxidation. With presented protocols, authors are able to provide conclusions regarding, e.g., complex I impairment, phosphorylation system limitation (3.2) mitochondrial content (3.3), leak respiration involvement, etc., besides OXPHOS and ETS capacities. Authors use their own terminology describing respiratory states. It would be useful to explain briefly their terminology also in terms of the canonical state 2 - 4 terminology. In spite of this, the methodology approach and presented data are well explained."