Altered Energy Transfer from Mitochondria to Sarcoplasmic Reticulum After Cytoarchitectural Perturbations in Mice Hearts.
From: U-769 INSERM, Châtenay-Malabry, France.
The Journal of physiology
- Publish Date: Aug 2006
- ISSN: 0022-3751
- Volume: 575
- Issue: Pt 1
- Pages: 191-200
- Medium: Print
- Language: English
- Citation (JAMA): Wilding James R, Joubert Frédéric, de Araujo Carla, et al. Altered Energy Transfer from Mitochondria to Sarcoplasmic Reticulum After Cytoarchitectural Perturbations in Mice Hearts.. J. Physiol. (Lond.) Aug 2006;575:191-200
Abstract
Sarcoplasmic reticulum (SR) calcium pump function requires a high local ATP/ADP ratio, which can be maintained by direct nucleotide channelling from mitochondria, and by SR-bound creatine kinase (CK)-catalysed phosphate-transfer from phosphocreatine. We hypothesized that SR calcium uptake supported by mitochondrial direct nucleotide channelling, but not bound CK, depends on the juxtaposition of these organelles. To test this, we studied a well-described model of cytoarchitectural disorganization, the muscle LIM protein (MLP)-null mouse heart. Subcellular organization was characterized using electron microscopy, and mitochondrial, SR and myofibrillar function were assessed in saponin-permeabilized fibres by measuring respiration rates and caffeine-induced tension transients. MLP-null hearts had fewer, less-tightly packed intermyofibrillar mitochondria, and more subsarcolemmal mitochondria. The apparent mitochondrial Km for ADP was significantly lower in the MLP-null heart than in control (175 +/- 15 and 270 +/- 33 microM, respectively), indicating greater ADP accessibility, although maximal respiration rate, mitochondrial content and total CK activity were unaltered. Active tension in the myofibres of MLP-null mice was 54% lower than in controls (39 +/- 3 and 18 +/- 1 mN mm(-2), respectively), consistent with cytoarchitectural disorganization. SR calcium loading in the myofibres of MLP-null mice was similar to that in control myofibres when energy support was provided via Bound CK, but approximately 36% lower than controls when energy support was provided by mitochondrial (P < 0.05). Mitochondrial support for SR calcium uptake was also specifically decreased in the desmin-null heart, which is another model of cytoarchitectural perturbation. Thus, despite normal oxidative capacity, direct nucleotide channelling to the SR was impaired in MLP deficiency, concomitant with looser mitochondrial packing and increased nucleotide accessibility to this organelle. Changes in cytoarchitecture may therefore impair subcellular energy transfer and contribute to energetic and contractile dysfunction.
Mesh Headings (Keywords): Adenosine Diphosphate, Animals, Calcium, Creatine Kinase, MB Form, Desmin, Energy Metabolism, Energy Transfer, Heart, Kinetics, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Heart, Models, Animal, Muscle Proteins, Myocardial Contraction, Myocardium, Myofibrils, Sarcoplasmic Reticulum
Check for Full Text / PubMed Unique Identifier (PMID): 16740607
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.