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首页> 外文期刊>Neuron >Aberrant Schwann cell lipid metabolism linked to mitochondrial deficits leads to axon degeneration and neuropathy.
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Aberrant Schwann cell lipid metabolism linked to mitochondrial deficits leads to axon degeneration and neuropathy.

机译：与线粒体缺陷相关的雪旺细胞脂代谢异常导致轴突变性和神经病。

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Mitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells [SCs]) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response (ISR) through the actions of heme-regulated inhibitor (HRI) kinase, and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines (ACs), an intermediate of fatty acid β-oxidation. Importantly, we show that ACs are released from SCs and induce axonal degeneration. A maladaptive ISR as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies.
机译：线粒体功能障碍是周围神经病变的常见原因。已经投入了大量的精力来研究神经元/轴突线粒体的作用，但是周围神经胶质细胞（Schwann细胞[SCs]）中的线粒体缺陷如何导致周围神经疾病仍不清楚。在这里，我们调查了继发于SC线粒体功能障碍（Tfam-SCKOs）的周围神经病变的小鼠模型。我们显示，SC线粒体的破坏通过血红素调节的抑制剂（HRI）激酶的作用激活了适应不良的综合应激反应（ISR），并引起脂质代谢从脂肪酸合成向氧化的转变。 SC脂质代谢中的这些改变导致重要的髓磷脂脂质成分的消耗以及酰基肉碱（ACs）（脂肪酸β-氧化的中间产物）的积累。重要的是，我们表明AC从SC中释放出来并引起轴突变性。因此，适应不良的ISR以及SC脂质代谢的改变是线粒体相关周围神经病变的潜在病理机制。

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