Journal article

Rewiring of the Human Mitochondrial Interactome during Neuronal Reprogramming Reveals Regulators of the Respirasome and Neurogenesis

Mohamed Taha Moutaoufik, Ramy Malty, Shahreen Amin, Qingzhou Zhang, Sadhna Phanse, Alla Gagarinova, Mara Zilocchi, Larissa Hoell, Zoran Minic, Maria Gagarinova, Hiroyuki Aoki, Jocelyn Stockwell, Matthew Jessulat, Florian Goebels, Kirsten Broderick, Nichollas E Scott, James Vlasblom, Gabriel Musso, Bhanu Prasad, Eleonora Lamantea Show all

iScience | CELL PRESS | Published : 2019

Abstract

Mitochondrial protein (MP) assemblies undergo alterations during neurogenesis, a complex process vital in brain homeostasis and disease. Yet which MP assemblies remodel during differentiation remains unclear. Here, using mass spectrometry-based co-fractionation profiles and phosphoproteomics, we generated mitochondrial interaction maps of human pluripotent embryonal carcinoma stem cells and differentiated neuronal-like cells, which presented as two discrete cell populations by single-cell RNA sequencing. The resulting networks, encompassing 6,442 high-quality associations among 600 MPs, revealed widespread changes in mitochondrial interactions and site-specific phosphorylation during neurona..

View full abstract

University of Melbourne Researchers

Grants

Awarded by CIHR


Awarded by HSFC


Awarded by ARSACS Foundation Parkinson Society Canada


Awarded by National Institutes of Health


Funding Acknowledgements

We thank Dr. Khaled Aly for helpful discussions; the Centre for Applied Genomics facility and SPARC Bio-centre at the Hospital for Sick Children, Toronto, for their help with bulk RNA-seq and Seahorse XF analyzer; Vanderbilt University Medical Center for scRNA-seq; and "Cell lines and DNA Bank of Movement Disorders and Neurodegenerative Diseases" of the Telethon Network of Genetic Biobanks and the Euro-BioBank network for providing patient fibroblasts with CIV deficiency and mutations in NDUFS1/V1 and PINK1. M.T.M., R.M., J.V., and M.J. were supported by a Saskatchewan Health Research Foundation Postdoctoral Fellowship, and A.G. is supported by a Canadian Institutes of Health Research (CIHR) postdoctoral fellowship. M.B. is a CIHR New Investigator (MSH-130178). This work was supported by grants from HSFC Grant-in-Aid to F.S.C. (G-16-00014633), CIHR to L.J.F. (MOP-77688) and M.B. (MOP-125952; RSN-124512, 132191; FDN-154318), as well as the ARSACS Foundation Parkinson Society Canada (2014-673) and National Institutes of Health (R01GM106019) to M.B.