91 research outputs found
Cardiolipin, Mitochondria, and Neurological Disease
Over the past decade, it has become clear that lipid homeostasis is central to cellular metabolism. Lipids are particularly abundant in the central nervous system (CNS) where they modulate membrane fluidity, electric signal transduction, and synaptic stabilization. Abnormal lipid profiles reported in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI), are further support for the importance of lipid metablism in the nervous system. Cardiolipin (CL), a mitochondria-exclusive phospholipid, has recently emerged as a focus of neurodegenerative disease research. Aberrant CL content, structure, and localization are linked to impaired neurogenesis and neuronal dysfunction, contributing to aging and the pathogenesis of several neurodegenerative diseases, such as AD and PD. Furthermore, the highly tissue-specific acyl chain composition of CL confers it significant potential as a biomarker to diagnose and monitor the progression in several neurological diseases. CL also represents a potential target for pharmacological strategies aimed at treating neurodegeneration. Given the equipoise that currently exists between CL metabolism, mitochondrial function, and neurological disease, we review the role of CL in nervous system physiology and monogenic and neurodegenerative disease pathophysiology, in addition to its potential application as a biomarker and pharmacological target
I Undervalue You but I Need You: The Dissociation of Attitude and Memory Toward In-Group Members
In the present study, the in-group bias or in-group derogation among mainland Chinese was investigated through a rating task and a recognition test. In two experiments,participants from two universities with similar ranks rated novel faces or names and then had a recognition test. Half of the faces or names were labeled as participants' own university and the other half were labeled as their counterpart. Results showed that, for either faces or names, rating scores for out-group members were consistently higher than those for in-group members, whereas the recognition accuracy showed just the opposite. These results indicated that the attitude and memory for group-relevant information might be dissociated among Mainland Chinese
Neonatal Fc Receptor: From Immunity to Therapeutics
The neonatal Fc receptor (FcRn), also known as the Brambell receptor and encoded by Fcgrt, is a MHC class I like molecule that functions to protect IgG and albumin from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation by professional antigen presenting cells. Its function is evident in early life in the transport of IgG from mother to fetus and neonate for passive immunity and later in the development of adaptive immunity and other functions throughout life. The unique ability of this receptor to prolong the half-life of IgG and albumin has guided engineering of novel therapeutics. Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn
mTOR: from growth signal integration to cancer, diabetes and ageing
In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy
and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France
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
Rapeseed oil‑rich diet alters hepatic mitochondrial membrane lipid composition and disrupts bioenergetics
Diet is directly related with physiological alterations
occurring at a cell and subcellular level. However,
the role of diet manipulation on mitochondrial physiology
is still largely unexplored. Aiming at correlating diet with
alterations of mitochondrial membrane composition and
bioenergetics, Wistar-Han male rats were fed for 11, 22 and
33 days with a rapeseed oil-based diet and mitochondrial
bioenergetics, and membrane composition were compared
at each time point with a standard diet group. Considerable
differences were noticed in mitochondrial membrane lipid composition, namely in terms of fatty acyl chains and relative
proportions of phospholipid classes, the modified diet
inducing a decrease in the saturated to unsaturated molar
ratio and an increase in the phosphatidylcholine to phosphatidylethanolamine
molar ratio. Mass spectrometry lipid
analysis showed significant differences in the major species
of cardiolipin, with an apparent increased incorporation
of oleic acid as a result of exposure to the modified
diet. Rats fed the modified diet during 22 days showed
decreased hepatic mitochondrial state 3 respiration and
were more susceptible to Ca2+-induced transition pore
opening. Rapeseed oil-enriched diet also appeared to promote
a decrease in hydroperoxide production by the respiratory
chain, although a simultaneous decrease in vitamin E
content was detected. In conclusion, our data indicate that
the rapeseed oil diet causes negative alterations on hepatic
mitochondrial bioenergetics, which may result from membrane
remodeling. Such alterations may have an impact not
only on energy supply to the cell, but also on drug-induced
hepatic mitochondrial liabilities.The project was supported by the Foundation
for Science and Technology with FEDER/COMPETE/National
Budget funds (research grants PTDC/QUI–QUI/101409/2008 to P. J.
O., PTDC/QUI-BIQ/103001/2008 to A. S. J. and strategic grant PEst-
C/SAU/LA0001/2011to the CNC). J. P. M. and A. M. S. acknowledge
FCT for Ph.D. grants SFRH/BD/37626/2007 and PTDC/AGRALI/
108326/2008, respectively
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