Distinct Roles of Mitochondrial HIGD1A and HIGD2A in Respiratory Complex and Supercomplex Biogenesis.
Distinct Roles of Mitochondrial HIGD1A and HIGD2A in Respiratory Complex and Supercomplex Biogenesis.
复制标题
DOI：
10.1016/j.celrep.2020.107607
复制
发表时间：
2020-05
期刊：
影响因子：
8.8
通讯作者：
Alba Timón-Gómez;J. Garlich;R. Stuart;C. Ugalde;A. Barrientos
中科院分区：
文献类型：
--
作者：
Alba Timón-Gómez;J. Garlich;R. Stuart;C. Ugalde;A. Barrientos
线粒体呼吸链酶被组织成单独的复合物和超复合物，其生物起源仍有待充分理解。为了揭示人类缺氧诱导基因结构域家族蛋白质HIGD 1A和HIGD 2A在这些过程中的作用，我们产生并表征了HIGD敲除（KO）细胞系。我们表明，HIGD 2A控制和协调的隔离和supercomplexed复杂IV（CIV）的模块化组装作用于COX 3组装模块。相反，HIGD 1A通过支持UQCRFS 1的掺入来调节含有CIII和CIII的超复合物生物发生。HIGD 1A还与COX 4 -1和COX 5A CIV亚基聚集，并且当过表达时，抑制HIGD 2A-KO细胞的CIV生物发生缺陷。我们得出的结论是，HIGD 1A和HIGD 2A在呼吸复合体和超复合体的生物发生中既具有独立的功能，又具有重叠的功能。我们的数据阐明了存在多种途径来组装这些结构的动态高介导的CIV生物合成，有可能适应不断变化的环境和营养条件。
The mitochondrial respiratory chain enzymes are organized as individual complexes and supercomplexes, whose biogenesis remains to be fully understood. To disclose the role of the human Hypoxia Inducible Gene Domain family proteins HIGD1A and HIGD2A in these processes, we generate and characterizeHIGD-knockout (KO) cell lines. We show that HIGD2A controls and coordinates the modular assembly of isolated and supercomplexed complex IV (CIV) by acting on the COX3 assembly module. In contrast, HIGD1A regulates CIII and CIII-containing supercomplex biogenesis by supporting the incorporation of UQCRFS1. HIGD1A also clusters with COX4-1 and COX5A CIV subunits and, when overexpressed, suppresses the CIV biogenesis defect ofHIGD2A-KO cells. We conclude that HIGD1A and HIGD2A have both independent and overlapping functions in the biogenesis of respiratory complexes and supercomplexes. Our data illuminate the existence of multiple pathways to assemble these structures by dynamic HIGD-mediated CIV biogenesis, potentially to adapt to changing environmental and nutritional conditions.