Nanoscopic quantification of sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells derived from patients with mitochondrial diseases

Journal of Nanobiotechnology

Jiajie Diao¹  Qixin Chen²  Weiwei Zou³  Jesse Slone⁴  Taosheng Huang⁴  Li Yang⁵  Xiaoting Lou⁶ 

[1] Department of Cancer Biology, University of Cincinnati College of Medicine, 45267, Cincinnati, OH, USA;Department of Cancer Biology, University of Cincinnati College of Medicine, 45267, Cincinnati, OH, USA;Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, 250062, Jinan, China;Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA;Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, 230022, Hefei, China;Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA;Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, 14203, Buffalo, NY, USA;Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA;Department of Pediatrics, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China;Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH, USA;School of Laboratory Medicine and Life sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China;

关键词: Nanoscope;    Mitochondrial disease;    SLC25A46;    Cristae;    Mitophagy;   

DOI  :  10.1186/s12951-021-00882-9

来源: Springer

【 摘 要 】

SLC25A46 mutations have been found to lead to mitochondrial hyper-fusion and reduced mitochondrial respiratory function, which results in optic atrophy, cerebellar atrophy, and other clinical symptoms of mitochondrial disease. However, it is generally believed that mitochondrial fusion is attributable to increased mitochondrial oxidative phosphorylation (OXPHOS), which is inconsistent with the decreased OXPHOS of highly-fused mitochondria observed in previous studies. In this paper, we have used the live-cell nanoscope to observe and quantify the structure of mitochondrial cristae, and the behavior of mitochondria and lysosomes in patient-derived SLC25A46 mutant fibroblasts. The results show that the cristae have been markedly damaged in the mutant fibroblasts, but there is no corresponding increase in mitophagy. This study suggests that severely damaged mitochondrial cristae might be the predominant cause of reduced OXPHOS in SLC25A46 mutant fibroblasts. This study demonstrates the utility of nanoscope-based imaging for realizing the sub-mitochondrial morphology, mitophagy and mitochondrial dynamics in living cells, which may be particularly valuable for the quick evaluation of pathogenesis of mitochondrial morphological abnormalities.

【 授权许可】

CC BY