MedicalResearch.com Interview with:
Alicia J. Kowaltowski, MD, PhD
Professor of Biochemistry
Departamento de Bioquímica, IQ, Universidade de São Paulo
São Paulo, SP, Brazil
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We recently found that brain mitochondria from calorically-restricted animals can take up more calcium than mitochondria from animals that eat ad libitum (or “all they can eat”; doi: 10.1111/acel.12527). Calcium is a well-know regulator of energy metabolism, as is caloric intake, but this was the first evidence that limiting caloric intake changed calcium handling by mitochondria, the main hub for energy metabolism. As a result, we decided to investigate if this result was specific for the brain or happened in other tissues, focusing on the liver because of its central importance in metabolic control.
We found that liver mitochondria from calorically-restricted mice take up substantially more calcium than ad libitum fed mice. We also found that this result is related to a change in the amount of ATP within the mitochondria; ATP can complex calcium ions effectively due to its negative charges. Finally, we were able to correlate the increase in calcium uptake by liver mitochondria to a very strong protection of caloric restriction livers against ischemia/reperfusion damage.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: We have uncovered a new mechanism in which the prevention of obesity by caloric restriction occurs: the increase in the speed and capacity for mitochondrial calcium accumulation. This means that mitochondrial calcium is important and should be considered when studying the effects of dietary interventions.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We have many questions based on these findings, including what these changes in mitochondrial calcium handling do under physiological conditions in terms of metabolic regulation, what the role of mitochondrial calcium is in metabolic responses in the brain and liver and what are the effects of caloric restriction and other dietary interventions on mitochondrial calcium handling in other tissues. We still have a lot of unanswered questions!
Disclosures: The studies were mostly conducted by Sergio Menezes-Filho, and excellent doctoral student in the lab, and included the collaboration of many other groups in the University of São Paulo. We are funded mainly by the CEPID-Redoxoma. No financial disclosures.
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Sergio L. Menezes-Filho, Ignacio Amigo, Fernanda M. Prado, Natalie C. Ferreira, Marcia K. Koike, Isabella F.D. Pinto, Sayuri Miyamoto, Edna F.S. Montero, Marisa H.G. Medeiros, Alicia J. Kowaltowski. Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca 2 -induced mitochondrial permeability transition. Free Radical Biology and Medicine, 2017; 110: 219 DOI: 10.1016/j.freeradbiomed.2017.06.013.
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