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Browsing Buenos Aires by Author "Czerniczyniec, Analía"
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    Response to the letter to the editor : mitochondria isolated from the striatum of the brain exhibit a higher degree of oxidative phosphorylation coupling, which shows that they are not subject to energetic dysfunction upon acute paraquat administration
    (Springer, 2016-9-29) Czerniczyniec, Analía ; Karadayian, Analía G. ; Bustamante, Juanita ; Lores-Arnaiz, Silvia
    In response to criticisms raised by Professor Rendon regarding our original study “Impairment of striatal mitochondrial function by acute paraquat poisoning” (J Bioenerg Biomembr 47:395–408, 2015), we re-evaluated key methodological aspects and data interpretation. Oxygen consumption rates were measured in the absence and presence of KCN (1.3 mM) and diphenyleneiodonium (DPI, 1 µM) to discriminate KCN-sensitive respiration from paraquat redox cycling. Paraquat inhibited state 4 and state 3 KCN-sensitive respiration by 80% and 62%, respectively, while DPI-sensitive oxygen uptake increased 2.2- to 2.3-fold, confirming both respiratory-chain inhibition and redox-cycling contributions. Respiratory control ratios were deliberately omitted for KCN-sensitive data, as they do not accurately reflect mitochondrial viability under these conditions; instead, direct analysis of metabolic states 4 and 3 revealed clear bioenergetic impairment. Submitochondrial membrane preparations were tested for vesicle formation using FCCP (4 µM); no stimulation of NADH-cytochrome c reductase, succinate-cytochrome c reductase, or cytochrome oxidase activities occurred, and paraquat-induced inhibition (27% in complex I–III and 19% in complex IV) persisted unchanged. Rotenone (3 µM) inhibited NADH-cytochrome c reductase by ~80% in both control and paraquat samples, confirming that measured activity was predominantly rotenone-sensitive complex I–III (32% inhibition by paraquat). These additional controls validate our original methodology and support the conclusion that acute paraquat poisoning impairs striatal mitochondrial bioenergetics through direct respiratory-chain inhibition and increased free-radical production.