Letter to the Editor: Dynamic SERCA regulation and early metabolic dysfunction in young adults with high waist-to-height ratio

Figure 1 The biphasic role of SERCA and the endoplasmic reticulum stress signaling pathway in the progression of metabolic dysfunction. The schematic illustrates the transition from an early adaptive phase to a progressive maladaptive stage in platelets. Early adaptive stage: In response to initial metabolic stress, platelets undergo compensatory upregulation of SERCA expression, facilitating efficient Ca²⁺ sequestration into the endoplasmic reticulum (ER) to maintain homeostasis and promote cell survival. Progressive dysfunction stage: Persistent metabolic overload leads to SERCA dysfunction and Ca²⁺ depletion in the ER lumen, causing cytosolic Ca²⁺ overload. This triggers maladaptive unfolded protein response activation, characterized by sustained PERK phosphorylation and JNK. ER: Endoplasmic reticulum; UPR: Unfolded protein response.