000			nab a22 7a 4500
999			_c18007 _d18007
003			PC18007
005			20250627131919.0
008			250627b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_91906 _aSánchez Aragó, María _eInstituto de Investigación i+12
245	0	0	_aMitochondrial response to the BCKDK-deficiency: Some clues to understand the positive dietary response in this form of autism. _h[artículo]
260			_bBiochimica et biophysyca acta, _c2016
300			_a1862(4):592-600.
500			_aFormato Vancouver: Oyarzabal A, Bravo Alonso I, Sánchez Aragó M, Rejas MT, Merinero B, García Cazorla A et al. Mitochondrial response to the BCKDK-deficiency: Some clues to understand the positive dietary response in this form of autism. Biochim Biophys Acta. 2016 Apr;1862(4):592-600.
501			_aPMID: 26809120.
504			_aContiene 39 referencias
520			_aMutations 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 dynamic 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 give 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.
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc18007.pdf _ySolicitar documento
942			_2ddc _cART _n0