Visualization of Submitochondrial Protein Distributions

Apoptotic effectors in the intermembrane mitochondrial space – insights by STED nanoscopy


By allowing visualization of submitochondrial protein distributions, fluorescence nanoscopy offers significant advantages for understanding cell death control. How cells manage, and control mitochondrial intermembrane proteins involved in apoptosis, such as Cytochrome c and DIABLO/SMAC is not completely defined. In this study, we used two-color STED nanoscopy to gain insight into the submitochondrial distribution of Cytochrome c and DIABLO/SMAC, two apoptotic effectors. Proteotoxic stress was used to induce cell death in leiomyosarcoma cells. STED microscopy allowed to reveal a cluster organization of DIABLO/SMAC distribution compared to the uniform distribution of ATP synthase. These clusters sometimes co-localize with clusters containing Cytochrome c. In conclusion, within the intermembrane space of mitochondria different storages of pro-death effectors exist.

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Iuliano L., Drioli S., Pignochino Y., Cafiero C.M., Minisini M., D'Este F., Picco R., Dalla E., Giordano G., Grignani G., Di Giorgio E., Benedetti F., Felluga F. and Brancolini C.:

Enhancing Proteotoxic Stress in Leiomyosarcoma Cells Triggers Mitochondrial Dysfunctions, Cell Death, and Antitumor Activity in vivo

DOI: 10.1158/1535-7163.MCT-20-0521 Published June 2021

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