In the Right Place at the Right Time: Regulation of Cell Metabolism by IP3R-Mediated Inter-Organelle Ca2+ Fluxes

Ahumada-Castro, Ulises; Bustos, Galdo; Silva-Pavez, Eduardo; Puebla-Huerta, Andrea; Lovy, Alenka; Cárdenas, César

doi:10.3389/fcell.2021.629522

Cited by 32 publications

(23 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The interaction between the ER and mitochondria is one of the most studied interactions in which IP3R-mediated Ca 2+ release plays a central role. 36 Ca 2+ signals originating from IP3R activation regulate multiple cellular processes including apoptosis and autophagy. 37 Besides, ER-mitochondria Ca 2+ exchange may regulate the mitochondrial dynamics response.…”

Section: Discussionmentioning

confidence: 99%

The fasting‐feeding metabolic transition regulates mitochondrial dynamics

et al. 2021

View full text Add to dashboard Cite

In humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75-g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate-treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R-mediated mitochondrial Ca 2+ accumulation. This allowed us to evaluate the role of ER-mitochondria Ca 2+ exchange in the mitochondrial dynamic response to substrate availability.

show abstract

Section: Discussionmentioning

confidence: 99%

The fasting‐feeding metabolic transition regulates mitochondrial dynamics

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In particular, the increased availability of Ca 2+ into the cytosol, from extracellular Ca 2+ influx and/or Ca 2+ release from intracellular stores, is essential to generate contraction in both striated and smooth muscles. Therefore, cytosolic Ca 2+ levels are tightly buffered, which largely results from this ion being sequestered in intracellular organelles that include the endo/sarcoplasmic reticulum (ER/SR), mitochondria and lysosomes (34)(35)(36)(37)(38)(39)(40).…”

Section: Muscle Types and Their Mechanisms For Contractionmentioning

confidence: 99%

“…Inositol 1,4,5-trisphosphate receptors (IP 3 R) and ryanodine receptors (RyR) are the main intracellular Ca 2+ release channels embedded in the ER/SER membranes (34,(36)(37)(38). Both receptor families evolved from a common ancestor and share ∼40% homology (34,35). Moreover, both receptor types form large homo-tetrameric complexes when inserted into membranes.…”

Section: Muscle Types and Their Mechanisms For Contractionmentioning

confidence: 99%

“…In turn, the main targets of IP 3 R-mediated Ca 2+ release are the mitochondria, which in turn regulates cell metabolism, lysosome activity and autophagy. IP 3 R is modulated by a canonical IP 3 R signaling pathway along with other regulatory proteins (34)(35)(36)(37).…”

Section: Muscle Types and Their Mechanisms For Contractionmentioning

confidence: 99%

“…In smooth muscle, both IP 3 Rs and RyRs participate in Ca 2+ -release and muscle contraction, via mechanisms comparable to the CICR utilized by cardiomyocytes (Figure 3) (34)(35)(36)(37)(38)(39)(40)(48)(49)(50). In vascular smooth muscle, however, the close vicinity between sarcoplasmic RyR2 (and likely RyR3 as well) and Ca 2+ /voltage-gated K + channels of big conductance (BK channels) located in the sarcolemma leads to BK channel-mediated Spontaneous Transient Outward Currents (STOCs), which oppose depolarization, blunt Ca 2+ -influx and thus, oppose smooth muscle contraction while enabling myocyte relaxation and vasodilation.…”

Section: E-c Coupling In Striated Muscle and Smooth Muscle Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Alcohol Use Disorders and Their Harmful Effects on the Contractility of Skeletal, Cardiac and Smooth Muscles

Alleyne¹,

Dopico²

2021

Adv. Drug Alcohol Res.

View full text Add to dashboard Cite

Alcohol misuse has deleterious effects on personal health, family, societal units, and global economies. Moreover, alcohol misuse usually leads to several diseases and conditions, including alcoholism, which is a chronic condition and a form of addiction. Alcohol misuse, whether as acute intoxication or alcoholism, adversely affects skeletal, cardiac and/or smooth muscle contraction. Ethanol (ethyl alcohol) is the main effector of alcohol-induced dysregulation of muscle contractility, regardless of alcoholic beverage type or the ethanol metabolite (with acetaldehyde being a notable exception). Ethanol, however, is a simple and “promiscuous” ligand that affects many targets to mediate a single biological effect. In this review, we firstly summarize the processes of excitation-contraction coupling and calcium homeostasis which are critical for the regulation of contractility in all muscle types. Secondly, we present the effects of acute and chronic alcohol exposure on the contractility of skeletal, cardiac, and vascular/ nonvascular smooth muscles. Distinctions are made between in vivo and in vitro experiments, intoxicating vs. sub-intoxicating ethanol levels, and human subjects vs. animal models. The differential effects of alcohol on biological sexes are also examined. Lastly, we show that alcohol-mediated disruption of muscle contractility, involves a wide variety of molecular players, including contractile proteins, their regulatory factors, membrane ion channels and pumps, and several signaling molecules. Clear identification of these molecular players constitutes a first step for a rationale design of pharmacotherapeutics to prevent, ameliorate and/or reverse the negative effects of alcohol on muscle contractility.

show abstract

HSP70 protects H9C2 cells from hypoxia and reoxygenation injury through STIM1/IP3R

Liu

Juan

Xia

et al. 2022

Cell Stress and Chaperones

View full text Add to dashboard Cite

Hypoxia/reoxygenation (H/R) is used as an in vivo model of ischemia/reperfusion injury, and myocardial ischemia can lead to heart disease. Calcium overload is an important factor in myocardial ischemia–reperfusion injury and can lead to apoptosis of myocardial cells. Therefore, it is of great clinical importance to find ways to regulate calcium overload and reduce apoptosis of myocardial cells, and thus alleviate myocardial ischemia–reperfusion injury. There is evidence that heat shock protein 70 (HSP70) has a protective effect on the myocardium, but the exact mechanism of this effect is not completely understood. Stromal interaction molecule 1 and inositol 1,4,5-triphosphate receptor (STIM/1IP3R) play an important role in myocardial ischemia–reperfusion injury. Therefore, this study aimed to investigate whether HSP70 plays an anti-apoptotic role in H9C2 cardiomyocytes by regulating the calcium overload pathway through STIM1/IP3R. Rat H9C2 cells were subjected to transient oxygen and glucose deprivation (incubated in glucose-free medium and hypoxia for 6 h) followed by re-exposure to glucose and reoxygenation (incubated in high glucose medium and reoxygenation for 4 h) to simulate myocardial ischemia reperfusion-induced cell injury. H9C2 cell viability was significantly decreased, and lactate dehydrogenase (LDH) release and apoptosis were significantly increased after oxygen and glucose deprivation. Transfection of HSP70 into H9C2 cells could reduce the corresponding effect, increase cell viability and anti-apoptotic signal pathway, and reduce the apoptotic rate and pro-apoptotic signal pathway. After hypoxia and reoxygenation, the expression of STIM1/IP3R and intracellular calcium concentration of HSP70-overexpressed H9C2 cells were significantly lower than those of hypoxia cells. Similarly, direct silencing of STIM1 by siRNA significantly increased cell viability and expression of anti-apoptotic protein Bcl-2 and decreased apoptosis rate and expression of pro-apoptotic protein BAX. These data are consistent with HSP70 overexpression. These results suggest that HSP70 abrogates intracellular calcium overload by inhibiting upregulation of STIM1/IP3R expression, thus reducing apoptosis in H9C2 cells and playing a protective role in cardiomyocytes.

show abstract

In the Right Place at the Right Time: Regulation of Cell Metabolism by IP3R-Mediated Inter-Organelle Ca2+ Fluxes

Cited by 32 publications

References 119 publications

The fasting‐feeding metabolic transition regulates mitochondrial dynamics

The fasting‐feeding metabolic transition regulates mitochondrial dynamics

Alcohol Use Disorders and Their Harmful Effects on the Contractility of Skeletal, Cardiac and Smooth Muscles

HSP70 protects H9C2 cells from hypoxia and reoxygenation injury through STIM1/IP3R

Contact Info

Product

Resources

About