TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry

Area of Science:

• Cell Biology
• Molecular Biology
• Physiology

Background:

• Lysosomes are key organelles for cellular catabolism and exocytosis.
• Calcium (Ca2+) signaling is crucial for lysosomal trafficking and fusion.
• Transcription factor EB (TFEB) regulates genes involved in lysosomal biogenesis and exocytosis.

Purpose of the Study:

• To investigate the role of TFEB and lysosomes in intracellular calcium (Ca2+) homeostasis.
• To determine how TFEB modulates Ca2+ dynamics in the cytosol, endoplasmic reticulum (ER), and lysosomes.

Main Methods:

• Transient TFEB overexpression in HeLa cells.
• Measurement of cytosolic Ca2+ response following capacitative Ca2+ entry.
• Analysis of Ca2+ dynamics in the ER and lysosomes.
• Assessment of TFEB-dependent effects following lysosomal damage.

Main Results:

• TFEB overexpression reduced cytosolic Ca2+ levels during capacitative Ca2+ influx.
• TFEB enhanced ER re-uptake of calcium.
• Lysosomes exhibited increased Ca2+ buffering capacity upon TFEB modulation.
• Lysosomal damage abolished TFEB-dependent Ca2+ regulation in cytosol and ER.

Conclusions:

• Lysosomes may play a significant role in buffering intracellular Ca2+.
• TFEB influences cellular Ca2+ homeostasis through lysosomal mechanisms.
• These findings offer new insights into lysosomal function beyond catabolism.