| Full text | |
| Author(s): |
Vilas-Boas, Eloisa A.
;
Cabral-Costa, Joao Victor
;
Ramos, Vitor M.
;
da Silva, Camille C. Caldeira
;
Kowaltowski, Alicia J.
Total Authors: 5
|
| Document type: | Journal article |
| Source: | Journal of Biological Chemistry; v. 299, n. 3, p. 17-pg., 2023-02-10. |
| Abstract | |
Calcium (Ca2+) is a key regulator in diverse intracellular signaling pathways and has long been implicated in metabolic control and mitochondrial function. Mitochondria can actively take up large amounts of Ca2+, thereby acting as important intracellular Ca2+ buffers and affecting cytosolic Ca2+ transients. Excessive mitochondrial matrix Ca2+ is known to be deleterious due to opening of the mitochondrial permeability transition pore (mPTP) and consequent membrane potential dissipation, leading to mitochondrial swelling, rupture, and cell death. Moderate Ca2+ within the organelle, on the other hand, can directly or indirectly activate mitochondrial matrix enzymes, possibly impacting on ATP production. Here, we aimed to determine in a quantitative manner if extra- or intramitochondrial Ca2+ modulates oxidative phosphorylation in mouse liver mitochondria and intact hepatocyte cell lines. To do so, we monitored the effects of more modest versus supraphysiological increases in cytosolic and mitochondrial Ca2+ on oxygen consumption rates. Isolated mitochondria present increased respiratory control ratios (a measure of oxidative phosphorylation efficiency) when incubated with low (2.4 +/- 0.6 mu M) and medium (22.0 +/- 2.4 mu M) Ca2+ concentrations in the presence of complex I-linked substrates pyruvate plus malate and alpha-ketoglutarate, respectively, but not complex II-linked succinate. In intact cells, both low and high cytosolic Ca2+ led to decreased respiratory rates, while ideal rates were present under physiological conditions. High Ca2+ decreased mitochondrial respiration in a substrate-dependent manner, mediated by mPTP. Overall, our results uncover a Goldilocks effect of Ca2+ on liver mitochondria, with specific "just right" concentrations that activate oxidative phosphorylation. (AU) | |
| FAPESP's process: | 17/14713-0 - Mitochondrial Ca2+ Handling in the Central Nervous System and Energy Metabolism Regulation |
| Grantee: | João Victor Cabral Costa |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/18402-4 - Effects of mitochondrial calcium transport regulation in autophagic process of hepatocytes |
| Grantee: | Vitor de Miranda Ramos |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 21/02481-2 - Energy metabolism regulation by mitochondrial Ca2+ transport in the liver |
| Grantee: | Eloisa Aparecida Vilas Boas |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |