The Taz1p Transacylase Is Imported and Sorted into the Outer Mitochondrial Membrane via a Membrane Anchor Domain

Mutations in the mitochondrial transacylase tafazzin, Taz1p, in Saccharomyces cerevisiae cause Barth syndrome, a disease of defective cardiolipin remodeling. Taz1p is an interfacial membrane protein that localizes to both the outer and inner membranes, lining the intermembrane space. Pathogenic point mutations in Taz1p that alter import and membrane insertion result in accumulation of monolysocardiolipin. In this study, we used yeast as a model to investigate the biogenesis of Taz1p. We show that to achieve this unique topology in mitochondria, Taz1p follows a novel import pathway in which it crosses the outer membrane via the translocase of the outer membrane and then uses the Tim9p-Tim10p complex of the intermembrane space to insert into the mitochondrial outer membrane. Taz1p is then transported to membranes of an intermediate density to reach a location in the inner membrane. Moreover, a pathogenic mutation within the membrane anchor (V224R) alters Taz1p import so that it bypasses the Tim9p-Tim10p complex and interacts with the translocase of the inner membrane, TIM23, to reach the matrix. Critical targeting information for Taz1p resides in the membrane anchor and flanking sequences, which are often mutated in Barth syndrome patients. These studies suggest that altering the mitochondrial import pathway of Taz1p may be important in understanding the molecular basis of Barth syndrome.     

Seasonal changes in reproductive behavior in two ovariectomized female rhesus monkeys treated year-round with estradiol

Two ovariectomized female rhesus monkeys treated year-round with estradiol-filled capsules were used in hour-long behavioral tests with male rhesus monkeys both in and out of the normal breeding season. The study was designed primarily to test male hormonal responses to copulatory behavior and it was expected that behavior of the females would be essentially the same under both seasonal conditions. Several behaviors of the female, however, were found to fluctuate on a seasonal basis, namely (1) proximity to the male, (2) grooming of the male, (3) sexual presentations, and (4) threatening away (a form of sexual invitation). All of these behaviors, except proximity, were found to be positively correlated with the male partner's testosterone levels before and after the behavior test in the only test condition in which most males ejaculated. The preliminary suggestion is made that these females responded to some cue, either from the environment or from the males, that caused a change in their behavior between breeding and nonbreeding seasons despite the constant hormonal environment provided by the estradiol capsules. Since the same behaviors which were sensitive to seasonal effects were positively correlated with male testosterone levels, it is possible that the male's hormonal status affects affects female behavior.