title: Mitochondrial matrix calcium is an activating signal for hormone secretion.
abstract: Mitochondrial Ca(2+) signals have been proposed to accelerate oxidative metabolism and ATP production to match Ca(2+)-activated energy-consuming processes. Efforts to understand the signaling role of mitochondrial Ca(2+) have been hampered by the inability to manipulate matrix Ca(2+) without directly altering cytosolic Ca(2+). We were able to selectively buffer mitochondrial Ca(2+) rises by targeting the Ca(2+)-binding protein S100G to the matrix. We find that matrix Ca(2+) controls signal-dependent NAD(P)H formation, respiration, and ATP changes in intact cells. Furthermore, we demonstrate that matrix Ca(2+) increases are necessary for the amplification of sustained glucose-dependent insulin secretion in β cells. Through the regulation of NAD(P)H in adrenal glomerulosa cells, matrix Ca(2+) also acts as a positive signal in reductive biosynthesis, which stimulates aldosterone secretion. Our dissection of cytosolic and mitochondrial Ca(2+) signals reveals the physiological importance of matrix Ca(2+) in energy metabolism required for signal-dependent hormone secretion.
authors.affiliation: Department of Cell Physiology and Metabolism, University of Geneva, University Medical Center, Switzerland. andreas.wiederkehr@unige.ch
authors.forename: Andreas
authors.initials: A
authors.lastname: Wiederkehr
authors.forename: Gergo
authors.initials: G
authors.lastname: Szanda
authors.forename: Dmitry
authors.initials: D
authors.lastname: Akhmedov
authors.forename: Chikage
authors.initials: C
authors.lastname: Mataki
authors.forename: Claus W
authors.initials: CW
authors.lastname: Heizmann
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.forename: Tullio
authors.initials: T
authors.lastname: Pozzan
authors.forename: András
authors.initials: A
authors.lastname: Spät
authors.forename: Claes B
authors.initials: CB
authors.lastname: Wollheim
mesh_terms: D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010101:Oxygen Consumption; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000166:cytology / Q000378:metabolism
chemical_list: D064026:Calbindins; D007328:Insulin; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; D000450:Aldosterone; D009249:NADP; D005947:Glucose; D002118:Calcium