Components of calcium signaling in autophagy
Location
E4110
Document Type
Poster
Start Date
30-11-2023 12:15 PM
End Date
30-11-2023 12:55 PM
Description
Abstract
Macroautophagy (autophagy) is a process that packages and delivers unwanted cellular components to the lysosome for degradation to maintain homeostasis. Autophagy is strongly activated by nutrient starvation, such as found in myocardial ischemia or infarction. Starvation, mimicked experimentally by removal of extracellular amino acids, induces an increase in intracellular Ca2+ (operationally, SICS, starvation-induced Ca2+ signal) that is predicted to initiate many Ca2+-dependent activities of autophagy via interactions with its ubiquitous transducer calmodulin (CaM). The transient receptor potential mucolipin 1 (TRPML1) is an important lysosomal Ca2+ release channel that participates in organellar fusion and acidification, critical steps of autophagy. We recently showed that CaM is critical for autophagy. However, whether CaM regulates components of SICS and lysosomal Ca2+ release via TRPML1 is unknown.
Here, we report that SICS consists of both organellar Ca2+ release and extracellular Ca2+ entry. Molecular buffering of CaM using a fusion of two high-affinity CaM-binding proteins is associated with substantial increases in both components. Activation of TRPML1 using the agonist ML-SA1 triggers a small Ca2+ release signal and a large Ca2+ entry signals that are higher with CaM buffering at all ML-SA1 doses tested. Notably, increasing buffering of CaM in a multiplexed imaging system that simultaneously detects the CaM sequesters and measures Ca2+ responses is associated with increasingly larger lysosomal Ca2+ release via the TRPML1. These data clearly indicate that nutrient starvation triggers increases in intracellular Ca2+ via multiple sources and that CaM regulates all its components. The data also suggest that CaM may directly inhibit TRPML1.
Recommended Citation
Giles, Jennifer; Ferow, Abel; and Tran, Quang-Kim, "Components of calcium signaling in autophagy" (2023). DMU Research Symposium. 11.
https://digitalcommons.dmu.edu/researchsymposium/2023rs/2023abstracts/11
Components of calcium signaling in autophagy
E4110
Abstract
Macroautophagy (autophagy) is a process that packages and delivers unwanted cellular components to the lysosome for degradation to maintain homeostasis. Autophagy is strongly activated by nutrient starvation, such as found in myocardial ischemia or infarction. Starvation, mimicked experimentally by removal of extracellular amino acids, induces an increase in intracellular Ca2+ (operationally, SICS, starvation-induced Ca2+ signal) that is predicted to initiate many Ca2+-dependent activities of autophagy via interactions with its ubiquitous transducer calmodulin (CaM). The transient receptor potential mucolipin 1 (TRPML1) is an important lysosomal Ca2+ release channel that participates in organellar fusion and acidification, critical steps of autophagy. We recently showed that CaM is critical for autophagy. However, whether CaM regulates components of SICS and lysosomal Ca2+ release via TRPML1 is unknown.
Here, we report that SICS consists of both organellar Ca2+ release and extracellular Ca2+ entry. Molecular buffering of CaM using a fusion of two high-affinity CaM-binding proteins is associated with substantial increases in both components. Activation of TRPML1 using the agonist ML-SA1 triggers a small Ca2+ release signal and a large Ca2+ entry signals that are higher with CaM buffering at all ML-SA1 doses tested. Notably, increasing buffering of CaM in a multiplexed imaging system that simultaneously detects the CaM sequesters and measures Ca2+ responses is associated with increasingly larger lysosomal Ca2+ release via the TRPML1. These data clearly indicate that nutrient starvation triggers increases in intracellular Ca2+ via multiple sources and that CaM regulates all its components. The data also suggest that CaM may directly inhibit TRPML1.
