Department of Pathology, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
Department of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama, USA.
J Cell Physiol. 2022 Nov;237(11):4049-4078. doi: 10.1002/jcp.30869. Epub 2022 Sep 8.
Mitochondria are pivotal organelles that govern cellular energy production through the oxidative phosphorylation system utilizing five respiratory complexes. In addition, mitochondria also contribute to various critical signaling pathways including apoptosis, damage-associated molecular patterns, calcium homeostasis, lipid, and amino acid biosynthesis. Among these diverse functions, the energy generation program oversee by mitochondria represents an immaculate orchestration and functional coordination between the mitochondria and nuclear encoded molecules. Perturbation in this program through respiratory complexes' alteration results in the manifestation of various mitochondrial disorders and malignancy, which is alarmingly becoming evident in the recent literature. Considering the clinical relevance and importance of this emerging medical problem, this review sheds light on the timing and nature of molecular alterations in various respiratory complexes and their functional consequences observed in various mitochondrial disorders and human cancers. Finally, we discussed how this wealth of information could be exploited and tailored to develop respiratory complex targeted personalized therapeutics and biomarkers for better management of various incurable human mitochondrial disorders and cancers.
线粒体是重要的细胞器,通过氧化磷酸化系统利用五个呼吸复合物来调节细胞的能量产生。此外,线粒体还参与各种关键的信号通路,包括细胞凋亡、损伤相关分子模式、钙稳态、脂质和氨基酸生物合成。在这些不同的功能中,线粒体所负责的能量产生程序代表了线粒体和核编码分子之间的完美协调和功能协调。通过呼吸复合物的改变干扰这个程序会导致各种线粒体疾病和恶性肿瘤的表现,这在最近的文献中变得明显。鉴于这个新兴医学问题的临床相关性和重要性,本综述阐明了各种呼吸复合物中分子改变的时间和性质,以及它们在各种线粒体疾病和人类癌症中观察到的功能后果。最后,我们讨论了如何利用这些丰富的信息来开发针对呼吸复合物的靶向个体化治疗和生物标志物,以更好地管理各种无法治愈的人类线粒体疾病和癌症。