Article

Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure

Department of Medicine, Obesity and Nutrition Section, Mitochondria ARC, Evans Biomedical Research Center, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA.
Cell metabolism (Impact Factor: 17.57). 04/2013; 17(4):491-506. DOI: 10.1016/j.cmet.2013.03.002
Source: PubMed

ABSTRACT

Mitochondrial fusion, fission, and mitophagy form an essential axis of mitochondrial quality control. However, quality control might not be the only task carried out by mitochondrial dynamics. Recent studies link mitochondrial dynamics to the balance between energy demand and nutrient supply, suggesting changes in mitochondrial architecture as a mechanism for bioenergetic adaptation to metabolic demands. By favoring either connected or fragmented architectures, mitochondrial dynamics regulates bioenergetic efficiency and energy expenditure. Placement of bioenergetic adaptation and quality control as competing tasks of mitochondrial dynamics might provide a new mechanism, linking excess nutrient environment to progressive mitochondrial dysfunction, common to age-related diseases.

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    • "This suggests dominant fission and fusion processes, respectively. Adaptations in mitochondrial shape, morphology and dynamics have been discussed as sensors for the control of energy demand and supply; more fragmented mitochondria have been associated with decreased function (reviewed by[46]). Other papers discussed mitochondrial dynamics briefly; Guo et al.[31]also observed more fragmented mitochondria in HFD groups after 30 weeks treatment (60% energy from fat, containing mainly lard). "

    Full-text · Dataset · Jan 2016
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    • "Recent studies have suggested that mitochondrial network architecture is the result of a dynamic process of continuous changes, through fusion and fission events, highly sensitive to metabolic cues, including nutrient utilization and energy expenditure[34,35]. Thus, we next explored if, associated to the bioenergetics depletion observed in the BCKDK-deficient fibroblasts, there was an adaptive response in their mitochondrial architecture. "
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    ABSTRACT: Mutations on the mitochondrial-expressed Branched Chain α-Keto acid Dehydrogenase Kinase (BCKDK) gene have been recently associated with a novel dietary-treatable form of autism. But, being a mitochondrial metabolism disease, little is known about the impact on mitochondrial performance. Here, we analyze the mitochondrial response to the BCKDK-deficiency in patient's primary fibroblasts by measuring bioenergetics, ultra-structural and dynamics parameters. A two-fold increase in superoxide anion production, together with a reduction in ATP-linked respiration and intracellular ATP levels (down to 60%) detected in mutants fibroblasts point to a general bioenergetics depletion that could affect the mitochondrial dynamics and cell fate. Ultrastructure analysis of BCKDK-deficient fibroblasts shows an increased number of elongated mitochondria, apparently associated with changes in the mediator of inner mitochondria membrane fusion, GTPase OPA1 forms, and in the outer mitochondrial membrane, mitofusin 2/MFN2. Our data support a possible hyperfusion response of BCKDK-deficient mitochondria to stress. Cellular fate also seems to be affected as these fibroblasts show an altered proportion of the cells on G0/G1 and G2/M phases. Knockdown of BCKDK gene in control fibroblasts recapitulates most of these features. Same BCKDK-knockdown in a MSUD patient fibroblasts unmasks the direct involvement of the accelerated BCAAs catabolism in the mitochondrial dysfunction. All these data gives us a clue to understand the positive dietary response to an overload of branched-chain amino acids. We hypothesize that a combination of the current therapeutic option with a protocol that considers the oxidative damage and energy expenditure, addressing the patients' individuality, might be useful for the physicians.
    Full-text · Article · Jan 2016 · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
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    • "This suggests dominant fission and fusion processes, respectively. Adaptations in mitochondrial shape, morphology and dynamics have been discussed as sensors for the control of energy demand and supply; more fragmented mitochondria have been associated with decreased function (reviewed by[46]). Other papers discussed mitochondrial dynamics briefly; Guo et al.[31]also observed more fragmented mitochondria in HFD groups after 30 weeks treatment (60% energy from fat, containing mainly lard). "
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    Full-text · Dataset · Jan 2016
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