Novel super-resolution capable mitochondrial probe, MitoRed AIE, enables assessment of real-time molecular mitochondrial dynamics.

Mitochondria and mitochondrial dynamics play vital roles in health and disease. With the intricate nanometer-scale structure and rapid dynamics of mitochondria, super-resolution microscopy techniques possess great un-tapped potential to significantly contribute to understanding mitochondrial biology and kinetics. Here we present a novel mitochondrial probe (MitoRed AIE) suitable for live mitochondrial dynamics imaging and single particle tracking (SPT), together with a multi-dimensional data analysis approach to assess local mitochondrial (membrane) fluidity. The MitoRed AIE probe localizes primarily to mitochondrial membranes, with 95 ms fluorophore on-time delivering 106 photons/ms, characteristics which we exploit to demonstrate live cell 100 fps 3D time-lapse tracking of mitochondria. Combining our experimental and analytical approaches, we uncover mitochondrial dynamics at unprecedented time scales. This approach opens up a new regime into high spatio-temporal resolution dynamics in many areas of mitochondrial biology.

Estrogen receptor ß activation impairs prostatic regeneration by inducing apoptosis in murine and human stem/progenitor enriched cell populations.

Androgen depletion is the primary treatment for prostate disease; however, it fails to target residual castrate-resistant cells that are regenerative and cells of origin of prostate cancer. Estrogens, like androgens, regulate survival in prostatic cells, and the goal of this study was to determine the advantages of selective activation of estrogen receptor ß (ERß) to induce cell death in stem cells that are castrate-resistant. Here we show two cycles of short-term ERß agonist (8ß-VE2) administration this treatment impairs regeneration, causing cystic atrophy that correlates with sustained depletion of p63+ basal cells. Furthermore, agonist treatment attenuates clonogenicity and self-renewal of murine prostatic stem/progenitor cells and depletes both murine (Lin(-)Sca1(+)CD49f(hi)) and human (CD49f(hi)Trop2(hi)) prostatic basal cells. Finally, we demonstrate the combined added benefits of selective stimulation of ERß, including the induction of cell death in quiescent post-castration tissues. Subsequent to castration ERß-induces further apoptosis in basal, luminal and intermediate cells. Our results reveal a novel benefit of ERß activation for prostate disease and suggest that combining selective activation of ERß with androgen-deprivation may be a feasible strategy to target stem cells implicated in the origin of prostatic disease.