Development

Heart regeneration in zebrafish. Poss, K. D. et al. Science 298, 2188–2190 (2002)

In most vertebrates, cardiac injury leads to scar formation. By contrast, zebrafish can regenerate cardiac tissue following mechanical injury, as is now shown by Mark Keating and colleagues. Cardiomyocyte proliferation occurs at the leading epicardial edge, and regeneration is complete within 2 months of 20% ventricular resection. However, zebrafish with a mutation in the Mps1 mitotic checkpoint kinase do not regenerate and form scar tissue.

Protein Translocation

Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Young, J. C. et al. Cell 112, 41–50 (2003)

The delivery of preproteins from the cytosol to mitochondria is poorly understood. Young et al. now report that, in mammals, the cytosolic chaperones Hsp90 and Hsp70 dock onto the import receptor Tom70 at the outer mitochondrial membrane. This interaction is essential for targeting a subset of preproteins to the receptor for subsequent import. However, in yeast, only Hsp70 docking is needed for effective preprotein delivery.

Bioenergetics

SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Piccard, F. et al. Cell 111, 931–941 (2002)

Piccard et al. found that two members of the p160 coregulator family — TIF2 and SRC-1 — have a function in the energy homeostasis of white and brown adipose tissues. TIF2−/− mice are protected against excessive fat accumulation and have increased insulin sensitivity. By contrast, SRC1−/− mice are prone to obesity due to reduced energy expenditure. These phenotypes are caused by changes in the expression ratio of TIF2 and SRC-1 leading to an altered composition of coregulator complexes, which, in turn, affects the transcriptional control of fat storage and thermogenesis.

Apoptosis

c-MYC apoptotic function is mediated by NRF-1 target genes.. Morrish, F. et al. Genes Dev. 17, 240–255 (2003)

Although earlier studies indicated a link with the mitochondrial apoptotic signalling pathway, the precise mechanism by which c-Myc induces apoptosis has remained elusive. Morrish et al. now show that c-Myc can stimulate target genes of the nuclear respiratory factor (NRF)-1, a transcription factor for several mitochondrial-related genes, including cytochrome c. Under conditions that trigger c-Myc-induced apoptosis, overexpression of NRF-1 sensitizes cells to apoptosis. Also, a dominant-negative NRF-1 mutant inhibits c-Myc-induced apoptosis but not c-Myc-induced proliferation.