What You Eat Affects Your Shape
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Mitochondria are no longer considered to be static structures that just make ATP. Emerging data show that mitochondrial form or shape is intimately related to mitochondrial function.1,2 It, therefore, follows that changes in mitochondrial substrate selection and metabolism might lead to altered mitochondrial dynamics. A recent study in Circulation Research examines this issue3
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Diabetic cardiomyopathy is associated with cardiac lipotoxicity and mitochondrial dysfunction,4 and a better understanding of the mechanisms involved are needed. To examine the mechanisms linking lipid overload and diabetic cardiomyopathy, Tsushima et al3 studied a mouse model with overexpression of ACSL1 (long-chain acyl-CoA synthetase 1) in cardiomyocytes (ACS-transgenic [Tg]). ACSL1 was under the control of α-myosin heavy chain promoter, and the gene was, therefore, turned on shortly before birth. Wild-type (WT) hearts had little or no ACSL1 mRNA expression at postnatal day zero (P0), whereas ACS-Tg hearts expressed mRNA but no protein at this time (P0). An increase in ACSL1 protein was observed in the ACS-Tg hearts at ≈1 week, and by 12 weeks, there was >10-fold increase in ACSL1 in the transgenic hearts. Normally, after birth, there is an increase in mitochondrial dimensions, and the mitochondria become larger. Interestingly, the postnatal increase in mitochondrial dimensions is blunted in the ACS-Tg hearts. Two-dimensional electron microscopy showed that in WT hearts, mitochondrial dimensions doubled by 3 weeks after birth; however, this postnatal increase was not observed in ASC-Tg mice. To better assess mitochondrial differences, 3-dimensional transmission electron microscopy tomography was performed, and data collected at 8 weeks showed that ACS-Tg mitochondria were narrower and more elongated than mitochondria from WT hearts. Thus, a role for alterations in proteins that regulate mitochondrial dynamics, the mitochondrial fission and fusion proteins, were considered.
As indicated by their names, these proteins regulate …