Evaluating the Bioenergetics Health Index Ratio in Leigh Syndrome Fibroblasts to Understand Disease Severity.
Evaluating the Bioenergetics Health Index Ratio in Leigh Syndrome Fibroblasts to Understand Disease Severity.
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评估Leigh综合征成纤维细胞的生物能量学健康指数比率以了解疾病的严重程度。
DOI：
10.3390/ijms221910344
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发表时间：
2021-09-26
影响因子：
5.6
通讯作者：
Iyer S
中科院分区：
文献类型：
--
作者：
Bakare AB;Dean J;Chen Q;Thorat V;Huang Y;LaFramboise T;Lesnefsky EJ;Iyer S
几种儿童线粒体疾病，包括Leigh综合征（LS），影响线粒体（mt）的遗传、发育和代谢，导致复杂的病理和能量衰竭。致病性mtDNA变异调节LS疾病严重程度的程度目前尚不清楚。为了更好地理解这种关系，我们计算了糖酵解生物能量健康指数（BHI），用于测量LS患者成纤维细胞的线粒体功能障碍，这些细胞含有不同百分比的致病突变mtDNA (T8993G, T9185C)，显示复合物V或复合物I （T10158C, T12706C）的缺乏。在影响复合体V的细胞中有高百分比（约90%）的致病mtDNA，而在影响复合体I的细胞中有低百分比（<39%）的致病mtDNA。电子传递链缺陷酶活性的水平与致病mtDNA的百分比相关。随后的生物能量学分析表明，细胞系依赖于OXPHOS和糖酵解来满足能量需求。结果表明，虽然LS的确切机制尚未阐明，但综合考虑特定致病mtDNA变异、糖酵解BHI和复合BHI（氧与糖酵解的平均比率）的多管齐下的方法可以帮助更好地了解影响LS疾病严重程度的因素。
Several pediatric mitochondrial disorders, including Leigh syndrome (LS), impact mitochondrial (mt) genetics, development, and metabolism, leading to complex pathologies and energy failure. The extent to which pathogenic mtDNA variants regulate disease severity in LS is currently not well understood. To better understand this relationship, we computed a glycolytic bioenergetics health index (BHI) for measuring mitochondrial dysfunction in LS patient fibroblast cells harboring varying percentages of pathogenic mutant mtDNA (T8993G, T9185C) exhibiting deficiency in complex V or complex I (T10158C, T12706C). A high percentage (>90%) of pathogenic mtDNA in cells affecting complex V and a low percentage (<39%) of pathogenic mtDNA in cells affecting complex I was quantified. Levels of defective enzyme activities of the electron transport chain correlated with the percentage of pathogenic mtDNA. Subsequent bioenergetics assays showed cell lines relied on both OXPHOS and glycolysis for meeting energy requirements. Results suggest that whereas the precise mechanism of LS has not been elucidated, a multi-pronged approach taking into consideration the specific pathogenic mtDNA variant, glycolytic BHI, and the composite BHI (average ratio of oxphos to glycolysis) can aid in better understanding the factors influencing disease severity in LS.
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影响因子：
6
作者：
Bakare AB;Rao RR;Iyer S
通讯作者：
Iyer S
影响因子：
3.9
作者：
Ganetzky, Rebecca D.;Stendel, Claudia;Falk, Marni J.
通讯作者：
Falk, Marni J.
影响因子：
15.9
作者：
Kirby, DM;Salemi, R;Thorburn, DR
通讯作者：
Thorburn, DR
影响因子：
3.7
作者：
Hill BG;Benavides GA;Lancaster JR Jr;Ballinger S;Dell'Italia L;Jianhua Z;Darley-Usmar VM
通讯作者：
Darley-Usmar VM
影响因子：
3.6
作者：
Crimi, M;Papadimitriou, A;Comi, GP
通讯作者：
Comi, GP