Cardio(lipin) workout beefs up mitochondrial imports

Cardio(lipin) workout beefs up mitochondrial impor ts Mitochondria depend on imported proteins. Kutik et al. show how a protein keeps this molecular traffi c fl owing by helping manufacture a key membrane lipid. Almost all of the 1,000 or so different proteins mitochondria need to operate are made elsewhere in the cell. After crossing a mitochondrion's outer membrane, proteins follow one of two routes through the organelle's inner membrane. In the carrier pathway, the protein complex TIM22 shepherds molecules into the inner membrane. The presequence pathway, by contrast, relies on the TIM23 complex. Researchers recently discovered that a protein called Tam41 was required for TIM23 to effi ciently import presequence molecules. Whether Tam41 also helped out in the carrier pathway was controversial. Kutik et al. used yeast devoid of Tam41 to answer the question. The researchers measured whether carrier-transported proteins combined into complexes, a sign that they'd arrived at their destination. The team found that in the mutant cells, the proteins often reached the inner membrane but didn't assemble into mature complexes. And the electrical potential that usually exists across the inner membrane dwindled. Those results suggest that not only is the presequence pathway faulty when Tam41 is missing, so is the carrier pathway. The mitochondrial defects resembled those caused by a scarcity of cardiolipin, an inner membrane lipid. Cardiolipin performs many jobs in mitochondria, including stabilizing the protein complexes involved in electron transport. Cardiolipin was almost absent from the mutant cells. Tam41 does not synthesize cardiolipin directly, but helps to fashion one of its precursors, the team found. Next task, the researchers say, is to identify that step. To keep transcribing, the genes that encode ribosomal RNA (rRNA) need to remain relaxed. Sanij et al. reveal how a transcription-promoting protein prevents these genes from getting uptight. Human cells have rRNA genes aplenty—roughly 200 of them, which are arranged in clusters. Tuning their output is crucial because too little rRNA can stifl e cell growth, whereas too much might lead to cancer. A factor that controls rRNA production is the protein UBF. It maintains rRNA genes in a loose conformation that allows transcription, rather than a condensed and inactive state. How UBF achieved this feat was an unanswered question. To fi nd out more, Sanij et al. used RNAi to trim UBF levels in human cells by 80%. The researchers' analysis ruled out one method that cells often employ to …