Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol accumulation that leads to early neurodegeneration in Niemann-Pick type C (NPC) disease. Mitochondria pathology and deficits in NPC1 deficient cells are associated with impaired lysosomal proteolysis and metabolic signaling. It is thought that activation of the transcription factor TFEB, an inducer of lysosome biogenesis, restores lysosomal-autophagy activity in lysosomal storage disorders. Here, we investigated the effect of trehalose, a TFEB activator, in the mitochondria pathology of NPC1 mutant fibroblasts
Lysosomes are multifunctional organelles involved in macromolecule degradation, nutrient sensing, and autophagy. Live imaging has revealed lysosome subpopulations with dynamics and characteristic cellular localization. An as‐yet unanswered question is whether lysosomes are spatially organized to coordinate and integrate their functions. Combined with super‐resolution microscopy, we designed a small organic fluorescent probe—TPAE—that targeted lysosomes with a large Stokes shift. When we analyzed the spatial organization of lysosomes against mitochondria in different cell lines with this probe, we discovered different distance distribution patterns between lysosomes and mitochondria during increased autophagy flux. By using
- Award ID(s):
- 1955358
- NSF-PAR ID:
- 10445420
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Exploration
- Volume:
- 2
- Issue:
- 3
- ISSN:
- 2766-2098
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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The present study supports the view that the cardiac mitoBKCachannel is functionally modulated by the BK‐β1 subunit; proper targeting and activation of mitoBKCashapes mitochondrial Ca2+handling.
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