Mitochondrial Dynamics and Mitochondria-Lysosome Contacts in Neurogenetic Diseases
In an article published in frontiers in Neuroscience, with the aim to study cellular phenotypes in fibroblasts from patients with neurogenetic diseases, Dr. Pijuan et.al. analyzed mitochondrial dynamics and mitochondria-lysosome contacts. Mitochondria make physical contact with other membranes in the cell and influence cell function.
In this post, we summarise the main conclusions of this article, showing that an interaction between Mitofusin 2 (Mfn2) of the outer mitochondrial membrane (OMM) protein and LAMP1 of the lysosome membrane protein was revealed, and Mfn2 defect impair the starvation-induced autophagy.
To study cellular phenotypes in fibroblasts from patients with neurogenetic diseases, Dr. Pijuan et.al. analyzed mitochondrial dynamics and mitochondria-lysosome contacts. Mitochondria make physical contact with other membranes in the cell and influence cell function. In this article, we introduce a report that an interaction between Mitofusin 2 (Mfn2) of the outer mitochondrial membrane (OMM) protein and LAMP1 of the lysosome membrane protein was revealed, and Mfn2 defect impair the starvation-induced autophagy.
The observation of morphological abnormalities in mitochondrial network was performed by fluorescent immunostaining. The mutated gene-specific morphological abnormalities were observed, and abnormalities in Mfn2, which is involved in the mitochondrial fusion process, cause an increase of the fragmentation of the mitochondrial network without the change in the mitochondrial mass. In addition, the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) were analyzed to confirm whether the mitochondrial network dysfunction affects mitochondrial activity and the generation of ROS. As a result, mitochondrial ROS increased while MMP did not change.
Moreover, proximity ligation assay (PLA) revealed an interaction between Mfn2 and LAMP1. Mfn2 mutations cause a significant reduction in the Mfn2-LAMP1 interaction. This result also indicated that Mfn2 is involved in mitochondria-lysosome contacts. The starvation-induced autophagy was impaired in patients’ fibroblasts with Mfn2 defects, but lysosomal morphology and function did not change. This suggests that Mfn2 mutation affects mitochondria-lysosome membrane contact sites. These results show a unique cellular phenotype of patients’ fibroblasts carrying pathogenic variants in the OMM protein Mfn2.
Figure 1: Cellular phenotypes in patients’ fibroblast with Mfn2 mutation.
This report suggests that the OMM protein Mfn2 is involved in mitochondria-lysosome membrane contact sites and regulates mitochondria-lysosome interactions as well as mitochondrial dynamics, and reveals a unique cellular phenotype in Mfn2 mutations. These findings indicate a relevance with Charcot-Marie-Tooth disease, which is one of the neuropathies. Accordingly, studying the interactions between organelles in neurogenetic diseases will be one of the interesting topics to be discussed in the future.
Keen to study the Mitochondria-Lysosome interactions?
Find out more about our partner Dojindo’s solutions for studying mitochondria and lysosomes in live and fixed cells.
Get access now to quick & easy solutions to study mitochondria and lysosomes in live and fixed cells, from our partner Dojindo, and push forward your research.
Reference
Pijuan J, Cantarero L, Natera-de Benito D, et al. Mitochondrial Dynamics and Mitochondria-Lysosome Contacts in Neurogenetic Diseases. Front Neurosci. 2022;16:784880. Published 2022 Jan 31. doi:10.3389/fnins.2022.784880
Acknowledgment
Special thanks to Ms. Yasuka Komatsu, our partner from Dojindo Laboratories, JAPAN, for writing this article.
