Mitochondrial Fusion in Drosophila Hearts (p 12)
Fusion of mitochondria is essential for function in cardiac myocytes, report Dorn et al.
Mitochondria periodically get together to exchange their contents. They do this by fusing both their inner and outer membranes under the control of particular membrane-bound proteins. The role of mitochondrial fusion in cardiomyocytes, where mitochondria make up a whopping 30% of the total volume, is not yet known. To investigate this, Dorn et al used RNAi to knock down the expression of two mitochondrial membrane-bound fusion regulators in the cardiac cells of flies. They found that loss of either protein led to defective fusion events—mitochondria were more heterogeneous in morphology and were, on average, approximately 30% smaller than in wild-type cells. Furthermore, the heart tube itself was dilated and displayed impaired contractility, suggesting that mitochondrial fusion is required for normal heart cell function. The defects could be prevented by excess superoxide dismutase, however. Because this enzyme removes reactive oxygen species, the authors conclude that free radicals are the damaging byproducts of the defective fusion events. In conclusion, proper mitochondrial fusion appears to be essential for preventing dilated cardiomyopathy in flies and, thus, perhaps in humans, too.
RISC Sequencing and In Vivo miR Targets (p 18)
In the hunt for heart-specific microRNA targets, Matkovich et al have refined their hunting tactics.
MicroRNAs (miRs) are small noncoding RNAs that bind to target mRNAs and suppress their expression by either tagging them for destruction or preventing their translation. In many cases, a single miR is capable of suppressing multiple mRNAs in the same cellular pathway, making them attractive target kingpins for therapies. Accurately identifying miR target mRNAs is not straightforward, however. Isolating target mRNAs from RISC—the protein complex where miRs and mRNAs interact—is one recently developed technique. But, the method requires the isolated mRNAs to be amplified before identification, which, say Matkovich et al, favors the isolation of certain mRNAs over others. The team has now refined the technique to avoid this amplification step, thus removing the bias. To find mRNAs associated with specific miRs, the team overexpressed cardiac-specific miR-133a and miR-499 in mouse hearts and used their new improved tool to compare RISC-associated mRNAs with total cell mRNAs. They identified 209 in vivo targets for miR-133a and 81 targets for miR-499. The new technique should be useful not only for identifying targets of native miRs, but also those of miRs designed for therapies, say the authors.
HKII in Ischemia/Reperfusion Injury (p 60)
Boosting glucose metabolism could help injured hearts to recover, say Wu et al.
It is well known that heart cells switch from fat metabolism to sugar metabolism (glycolysis) to increase available energy after ischemic injury. Wu et al, therefore, wondered whether altering the levels of glycolytic enzymes might affect recovery. One of the key rate-limiting enzymes of glycolysis is hexokinase (HK), of which four different isoforms exist in mammals—I, II, III, and IV. HKII is primarily expressed in both heart and skeletal muscle, so Wu and colleagues decided to start with this one. The team observed how HKII-deficient mouse hearts and wild-type mouse hearts, which are of similar size and function under normal conditions, fared after suffering an ischemic injury. HKII-deficient hearts were much worse off, displaying considerably reduced contractility and output after ischemia compared with wild-type hearts. This reduction in function was confirmed in isolated heart cells, in which a lack of HKII resulted in reduced ATP levels and contractility. HKII-deficient mice also suffered more extensive heart injury compared with wild types, with greater cell death and fibrosis and reduced postinjury angiogenesis. The authors suggest that increasing levels of HKII might be a new therapeutic option for decreasing ischemic injury to the heart.
Written by Ruth Williams
- © 2011 American Heart Association, Inc.