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The mammalian circadian clock uses interlocked negative feedback loops in which the heterodimeric basic helix-loop-helix transcription factor BMAL1/CLOCK is a master regulator. While there is prominent control of liver functions by the circadian clock, the detailed links between circadian regulators and downstream targets are poorly known. Using chromatin(More)
Tim23, an essential component of the protein import machinery of the inner membrane of mitochondria (TIM complex), forms dimers that display a dynamic behavior. Dimer formation is promoted by the membrane potential delta psi. Binding of a matrix targeting sequence to Tim23 triggers dimer dissociation. Monomeric Tim23 is present when a preprotein chain is in(More)
Members of the mitochondrial carrier family such as the ADP/ATP carrier (AAC) are composed of three structurally related modules. Here we show that each of the modules contains a mitochondrial import signal recognized by Tim10 and Tim12 in the intermembrane space. The first and the second module are translocated across the outer membrane independently of(More)
Fzo1p is a novel component required for the biogenesis of functional mitochondria in the yeast Saccharomyces cerevisiae. The protein is homologous to Drosophila Fzo, the first known protein mediator of mitochondrial fusion. Deletion of the FZO1 gene results in a petite phenotype, loss of mitochondrial DNA, and a fragmented mitochondrial morphology. Fzo1p is(More)
We have identified a complex in mitochondria that functions as a part of the preprotein import machinery of the inner membrane (MIM complex). Two known components, MIM23 and MIM17, and two novel components, MIM33 and MIM14, were found as constituents of this complex. In the presence of a translocating chain, the outer membrane import machinery (MOM complex)(More)
Proteins that are destined for the matrix of mitochondria are transported into this organelle by two translocases: the TOM complex, which transports proteins across the outer mitochondrial membrane; and the TIM23 complex, which gets them through the inner mitochondrial membrane. Two models have been proposed to explain how this protein-import machinery(More)
Tim23, a key component of the mitochondrial preprotein translocase, is anchored in the inner membrane by its C-terminal domain and exposes an intermediate domain in the intermembrane space that functions as a presequence receptor. We show that the N-terminal domain of Tim23 is exposed on the surface of the outer membrane. The two-membrane-spanning topology(More)
Circadian clocks are self-sustained oscillators modulating rhythmic transcription of large numbers of genes. Clock-controlled gene expression manifests in circadian rhythmicity of many physiological and behavioral functions. In eukaryotes, expression of core clock components is organized in a network of interconnected positive and negative feedback loops.(More)
The large (l) and small (s) isoforms of FREQUENCY (FRQ) are elements of interconnected feedback loops of the Neurospora circadian clock. The expression ratio of l-FRQ vs. s-FRQ is regulated by thermosensitive splicing of an intron containing the initiation codon for l-FRQ. We show that this splicing is dependent on light and temperature and displays a(More)
Anesthetic agents prolong cardiac repolarization by blocking ion currents. However, the clinical relevance of this blockade in subjects with reduced repolarization reserve is unknown. We have generated transgenic long QT syndromes type 1 (LQT1) and type 2 (LQT2) rabbits that lack slow delayed rectifier K+ currents (IKs) or rapidly activating K+ currents(More)