Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes.
Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes.
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DOI：
10.1038/s41586-023-06857-0
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发表时间：
2024-01
期刊：
影响因子：
64.8
通讯作者：
Pasparakis, Manolis
中科院分区：
文献类型：
--
作者：
Moschandrea, Chrysanthi;Kondylis, Vangelis;Evangelakos, Ioannis;Herholz, Marija;Schneider, Farina;Schmidt, Christina;Yang, Ming;Ehret, Sandra;Heine, Markus;Jaeckstein, Michelle Y.;Szczepanowska, Karolina;Schwarzer, Robin;Baumann, Linda;Bock, Theresa;Nikitopoulou, Efterpi;Brodesser, Susanne;Krueger, Marcus;Frezza, Christian;Heeren, Joerg;Trifunovic, Aleksandra;Pasparakis, Manolis
消化的膳食脂肪被肠细胞吸收，在那里它们在内质网中组装成前乳糜微粒，然后运输到高尔基体进行成熟，随后分泌到循环中。线粒体在膳食脂质加工中的作用尚不清楚。在这里，我们表明，肠上皮细胞的线粒体功能障碍抑制乳糜微粒的生产和运输的饮食脂质外周器官。在肠上皮细胞中特异性切除线粒体乙酰-tRNA合成酶DARS 2（参考文献）、呼吸链亚基SDHA或组装因子COX 10（参考文献）的小鼠显示，近端小肠的肠上皮细胞中积累了大脂滴（LD），并且未能茁壮成长。喂食无脂饮食抑制了DARS 2缺陷肠细胞中LD的积累，这表明积累的脂质主要来自消化的脂肪。此外，代谢追踪研究显示，在肠上皮细胞中缺乏DARS 2的小鼠中，饮食脂质向外周器官的转运受损。DARS 2缺陷导致明显缺乏成熟的乳糜微粒伴随着近端肠上皮细胞中高尔基体的逐渐分散。这一发现表明，线粒体功能障碍导致乳糜微粒从内质网到高尔基体的运输受损，这反过来又导致膳食脂质储存在大的细胞质LD中。总之，这些结果揭示了线粒体在肠上皮细胞中的膳食脂质转运中的作用，这可能与理解线粒体疾病患者中观察到的肠道缺陷有关。线粒体在肠上皮细胞中的膳食脂质转运中具有关键作用，这一发现可能与理解线粒体疾病患者的异常胃肠道功能有关。
Digested dietary fats are taken up by enterocytes where they are assembled into pre-chylomicrons in the endoplasmic reticulum followed by transport to the Golgi for maturation and subsequent secretion to the circulation. The role of mitochondria in dietary lipid processing is unclear. Here we show that mitochondrial dysfunction in enterocytes inhibits chylomicron production and the transport of dietary lipids to peripheral organs. Mice with specific ablation of the mitochondrial aspartyl-tRNA synthetase DARS2 (ref. ), the respiratory chain subunit SDHA or the assembly factor COX10 (ref. ) in intestinal epithelial cells showed accumulation of large lipid droplets (LDs) in enterocytes of the proximal small intestine and failed to thrive. Feeding a fat-free diet suppressed the build-up of LDs in DARS2-deficient enterocytes, which shows that the accumulating lipids derive mostly from digested fat. Furthermore, metabolic tracing studies revealed an impaired transport of dietary lipids to peripheral organs in mice lacking DARS2 in intestinal epithelial cells. DARS2 deficiency caused a distinct lack of mature chylomicrons concomitant with a progressive dispersal of the Golgi apparatus in proximal enterocytes. This finding suggests that mitochondrial dysfunction results in impaired trafficking of chylomicrons from the endoplasmic reticulum to the Golgi, which in turn leads to storage of dietary lipids in large cytoplasmic LDs. Taken together, these results reveal a role for mitochondria in dietary lipid transport in enterocytes, which might be relevant for understanding the intestinal defects observed in patients with mitochondrial disorders. Mitochondria have a pivotal role in the transport of dietary lipids in enterocytes, a finding that might have relevance to understanding the aberrant gastrointestinal function in patients with mitochondrial disorders.
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影响因子：
13.6
作者：
Kaspar S;Oertlin C;Szczepanowska K;Kukat A;Senft K;Lucas C;Brodesser S;Hatzoglou M;Larsson O;Topisirovic I;Trifunovic A
通讯作者：
Trifunovic A
影响因子：
21.3
作者：
通讯作者：
--
DOI：
10.1083/jcb.120.5.1123
发表时间：
1993-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Humphrey JS;Peters PJ;Yuan LC;Bonifacino JS
通讯作者：
Bonifacino JS
影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
30.8
作者：
BOURGERON, T;RUSTIN, P;ROTIG, A
通讯作者：
ROTIG, A