Mitochondrial  proteome Babu Lab

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

Moutaoufik et al. (2019)

• Mitochondrial (mt) protein (MP) assemblies undergo alterations during neurogenesis, a complex process vital in brain homeostasis and disease. Yet which mt macromolecular assemblies remodel during differentiation remains unclear. Here, using mass spectrometry-based co-fractionation profiles and phosphoproteomics, we generated mt interaction maps of human pluripotent embryonic carcinoma stem cells and terminally differentiated neurons. The resulting networks, encompassing 6,442 high-quality associations among 600 human MPs, revealed widespread changes in mt interactions and site-specific phosphorylation during neuronal differentiation. Besides elucidating interactions perturbed by complex I deficiency-associated alleles, we show C20orf24 as a respirasome assembly factor, whose disruption markedly reduces respiratory chain activity in complex IV-deficient patients. We also find a heme-containing neurotrophic factor, NENF, couples with Parkinson's disease-related proteins to promote neurotrophic activity. Our results provide new insights into the dynamic reorganization of mt networks during neuronal differentiation, and highlight novel mechanisms for MPs in respirasome, neuronal function, and mt diseases.


• From this website, you can access and download annotations, interactions, complexes and supplementary data for all Mitchondrial proteome proteins analyzed in this study.