Tight mitochondrial control of calcium and exocytotic signals in chromaffin cells at embryonic life

Abstract

Calcium buffering by mitochondria plays a relevant physiological function in the regulation of Ca(2+) and exocytotic signals in mature chromaffin cells (CCs) from various adult mammals. Whether a similar or different role of mitochondrial Ca(2+) buffering is present in immature CCs at early life has not been explored. Here we present a comparative study in rat embryonic CCs and rat mother CCs, of various physiological parameters that are known to be affected by mitochondrial Ca(2+) buffering during cell activation. We found that the clearance of cytosolic Ca(2+) transients ([Ca(2+)]c) elicited by high K(+) was 7-fold faster in embryo CCs compared to mother CCs. This strongly suggests that at embryonic life, the mitochondria play a more significant role in the clearance of [Ca(2+)]c loads compared to adult life. Consistent with this view are the following results concerning the transient suppression of mitochondrial Ca(2+) buffering by protonophore FCCP, in embryonic CCs compared to mother CCs: (i) faster and greater inactivation of inward calcium currents, (ii) higher K(+)-elicited [Ca(2+)]c transients with 25-fold faster clearance, (iii) higher increase of basal catecholamine release and (iv) higher potentiation of K(+)-evoked secretion. These pronounced differences could be explained by two additional features (embryo versus mother CCs): (a) slower recovery of mitochondrial resting membrane potential after the application of a transient FCCP pulse and (b) greater relative density of the mitochondria in the cytosol. This tighter control by the mitochondria of Ca(2+) and exocytotic signals may be relevant to secure a healthy catecholamine secretory response at early life.

Mitochondrial Ca2+ levels lower down rate of metabolic diseases and cardiomyopathies

“…It assists in production of energy, calcium buffering, all oxygen based physiological functions, and in regulation of Ca 2+ and exocytotic signals in mature cells ( Figure 1). 9 More often, Ca 2+ signals, integrate extracellular and intracellular fluxes, and play important role in synaptic plasticity and memory. These are also required for, neurotransmitter release, and neuronal excitability.…”

“…All mitochondrial dysfunctions cause impairment of the mitochondrial respiratory chain, generate excessive of reactive oxygen species, and induce excitotoxicity. 9 This disturbance in calcium uptake and release impose pathogenesis results in certain neurodegenerative diseases, neuropsychiatric disorders, and cancer. 2 Calcium release in neurons causes an instant increase in cytosolic and mitochondrial synchronization of electrical activity that start energy metabolism.…”

“…For normal functioning of cells and its metabolism calcium buffering is highly important because it is required for maintaining cell signaling. 9 Moreover, Cav1.1→CaMKII→NOS occurs in skeletal muscles regulate the intracellular distribution of the fatty acid lead by a transport protein CD36. It alters fatty acid metabolism.…”

“…14 Ca 2+ level in mitochondria and exocytotic signals are required for catecholamine secretory response. 9 Mitochondria both encode and decode Ca 2+ signals which largely put impact on cell signaling and metabolism. More specifically, a mitochondrial protein Fus1 a tumor suppressor effectively controls immune response and tumor growth via maintenance of mitochondrial homeostasis and Ca 2+ accumulation.…”