Complex I impairment in mitochondrial diseases and cancer: Parallel roads leading to different outcomes
Complex I impairment in mitochondrial diseases and cancer: Parallel roads leading to different outcomes
复制标题
DOI：
10.1016/j.biocel.2012.05.016
复制
发表时间：
2013-01-01
影响因子：
4
通讯作者：
Porcelli, Anna Maria
中科院分区：
文献类型：
--
作者：
Iommarini, Luisa;Calvaruso, Maria Antonietta;Porcelli, Anna Maria
呼吸链复合物I（CI）功能障碍已被认为是线粒体神经肌肉疾病的最常见原因之一。此外，最新的报告显示，氯损伤是许多其他病理过程，包括癌症的一个主要因素。事实上，能量消耗，氧化应激和代谢失衡往往与CI功能和结构的改变。线粒体DNA（mtDNA）突变的发生是神经肌肉疾病和癌症的共同特征;然而，两种不同的表型取决于突变类型（分解与非分解突变），突变负荷和细胞型。在这篇综述中，我们统一了我们的知识CI损伤所造成的结构CI基因和组装分子伴侣突变，无论是在线粒体疾病和癌症，分层这种突变的基础上，其功能与结构的影响。我们总结了共享和特定的代谢后果CI功能障碍在这些pathologies，这使我们能够绘制两个平行的道路，导致不同的临床outcomes.This文章的一部分，有针对性的问题，题为：生物能量功能障碍，适应和治疗。(C)2012爱思唯尔有限公司保留所有权利。
Respiratory chain complex I (CI) dysfunctions have been recognized as one of the most frequent causes of mitochondrial neuro-muscular disorders. Moreover, latest reports reveal that Cl impairment is a major contributing factor in many other pathological processes, including cancer. In fact, energy depletion, oxidative stress and metabolites unbalance are frequently associated with CI functional and structural alterations. The occurrence of mitochondrial DNA (mtDNA) mutations is a shared feature in neuromuscular diseases and cancer; however, the two diverging phenotypes arise depending on the mutation type (disassembling versus non-disassembling mutations), the mutant load and the cytotype. In this review, we unify our knowledge on CI impairment caused by mutations in structural CI genes and assembly chaperones, both in mitochondrial disorders and cancer, stratifying such mutations based on their functional versus structural effects. We summarize shared and specific metabolic consequences of CI dysfunction in these pathologies, which allow us to draw two parallel roads that lead to different clinical outcomes.This article is part of a Directed Issue entitled: Bioenergetic dysfunction, adaptation and therapy. (C) 2012 Elsevier Ltd. All rights reserved.