Differential remodelling of mitochondrial subpopulations and mitochondrial dysfunction are a feature of early stage diabetes.
Differential remodelling of mitochondrial subpopulations and mitochondrial dysfunction are a feature of early stage diabetes.
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DOI：
10.1038/s41598-022-04929-1
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发表时间：
2022-01-19
影响因子：
4.6
通讯作者：
Kitmitto A
中科院分区：
文献类型：
--
作者：
Rajab BS;Kassab S;Stonall CD;Daghistani H;Gibbons S;Mamas M;Smith D;Mironov A;AlBalawi Z;Zhang YH;Baudoin F;Zi M;Prehar S;Cartwright EJ;Kitmitto A
线粒体功能障碍是I型和II型糖尿病的一个特征，但报告之间缺乏一致性以及与疾病发展的联系。我们的目的是调查是否线粒体结构-功能重塑发生在糖尿病的早期阶段，采用小鼠模型（GENA 348）的成熟发病糖尿病的年轻人，表现出高血糖症，但不是高胰岛素血症，轻度左心室功能障碍。采用3-D电子显微镜（SBF-SEM），我们确定，与野生型WT相比，GENA 348肌膜下线粒体（SSM）大约2倍，与融合蛋白Mfn 1，Mfn 2和Opa 1的上调一致。此外，相比之下，GENA 348线粒体的形状更不规则，具有更多的管状突起，SSM突起更长更宽。GENA 348心肌中的线粒体密度也增加，与PGC 1-α上调和线粒体自噬停滞（PINK 1、Parkin和Miro 1下调）一致。GENA 348线粒体具有更不规则的嵴排列，但嵴尺寸和密度与WT相似。GENA 348复合物活性（I、II、IV、V）活性降低，但OCR增加，可能与糖酵解受损导致脂肪酸氧化转变有关。这些新的数据表明，在糖尿病的早期阶段，线粒体形态、动力学和功能失调。
Mitochondrial dysfunction is a feature of type I and type II diabetes, but there is a lack of consistency between reports and links to disease development. We aimed to investigate if mitochondrial structure–function remodelling occurs in the early stages of diabetes by employing a mouse model (GENA348) of Maturity Onset Diabetes in the Young, exhibiting hyperglycemia, but not hyperinsulinemia, with mild left ventricular dysfunction. Employing 3-D electron microscopy (SBF-SEM) we determined that compared to wild-type, WT, the GENA348 subsarcolemma mitochondria (SSM) are ~ 2-fold larger, consistent with up-regulation of fusion proteins Mfn1, Mfn2 and Opa1. Further, in comparison, GENA348 mitochondria are more irregular in shape, have more tubular projections with SSM projections being longer and wider. Mitochondrial density is also increased in the GENA348 myocardium consistent with up-regulation of PGC1-α and stalled mitophagy (down-regulation of PINK1, Parkin and Miro1). GENA348 mitochondria have more irregular cristae arrangements but cristae dimensions and density are similar to WT. GENA348 Complex activity (I, II, IV, V) activity is decreased but the OCR is increased, potentially linked to a shift towards fatty acid oxidation due to impaired glycolysis. These novel data reveal that dysregulated mitochondrial morphology, dynamics and function develop in the early stages of diabetes.
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DOI：
10.1083/jcb.201008084
发表时间：
2010-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jin SM;Lazarou M;Wang C;Kane LA;Narendra DP;Youle RJ
通讯作者：
Youle RJ
影响因子：
20.1
作者：
Bhandari P;Song M;Chen Y;Burelle Y;Dorn GW 2nd
通讯作者：
Dorn GW 2nd
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
7.7
作者：
Bach, D;Naon, D;Zorzano, A
通讯作者：
Zorzano, A
DOI：
10.1073/pnas.152259999
发表时间：
2002-07-23
影响因子：
11.1
作者：
Dzeja, PP;Bortolon, R;Terzic, A
通讯作者：
Terzic, A