Intracellular Membranes

Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The burden of protein misfolding is believed to contribute to aging. However, the links between adaptations to conditions associated with protein misfolding and resistance to the time-dependent attrition of cellular function remain poorly understood. We report that worms lacking aip-1, a homologue of mammalian AIRAP (arsenic-inducible proteasomal 19S regulatory particle-associated protein), are not only impaired in their ability to resist exposure to arsenite but also exhibit shortened lifespan and hypersensitivity to misfolding-prone proteins under normal laboratory conditions.

Author(s): 
Yun, Chi
Stanhill, Ariel
Yang, Yun
Zhang, Yuhong
Haynes, Cole M.
Xu, Chong-Feng
Neubert, Thomas A.
Mor, Adam
Philips, Mark R.
Ron, David
Publication Title: 
Annals of the New York Academy of Sciences

Hardly an aspect of aging is more important than an organism's ability to withstand stress or to resist both internally and externally imposed insults. We know that as organisms loose their ability to resist these insults, aged organisms suffer more than the young. Therefore, a prime strategy for an organism's survival has been the evolutionarily adapted defense systems that guard against insult. For better survivability, an organism's defense system must be maximized to its full effect through well-coordinated networks of diverse biologically responsive elements.

Author(s): 
Yu, B. P.
Chung, H. Y.
Publication Title: 
The EMBO journal

The P-glycoprotein homolog of the human malaria parasite Plasmodium falciparum (Pgh-1) has been implicated in decreased susceptibility to several antimalarial drugs, including quinine, mefloquine and artemisinin. Pgh-1 mainly resides within the parasite's food vacuolar membrane. Here, we describe a surrogate assay for Pgh-1 function based on the subcellular distribution of Fluo-4 acetoxymethylester and its free fluorochrome. We identified two distinct Fluo-4 staining phenotypes: preferential staining of the food vacuole versus a more diffuse staining of the entire parasite.

Author(s): 
Rohrbach, Petra
Sanchez, Cecilia P.
Hayton, Karen
Friedrich, Oliver
Patel, Jigar
Sidhu, Amar Bir Singh
Ferdig, Michael T.
Fidock, David A.
Lanzer, Michael
Publication Title: 
Science (New York, N.Y.)

Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis.

Author(s): 
Wei, M. C.
Zong, W. X.
Cheng, E. H.
Lindsten, T.
Panoutsakopoulou, V.
Ross, A. J.
Roth, K. A.
MacGregor, G. R.
Thompson, C. B.
Korsmeyer, S. J.
Publication Title: 
Human Molecular Genetics

Alzheimer's disease (AD) is a complex, neurodegenerative disease characterized by the impairment of cognitive function in elderly individuals. In a recent global gene expression study of APP transgenic mice, we found elevated expression of mitochondrial genes, which we hypothesize represents a compensatory response because of mitochondrial oxidative damage caused by the over-expression of mutant APP and/or amyloid beta (Abeta).

Author(s): 
Manczak, Maria
Anekonda, Thimmappa S.
Henson, Edward
Park, Byung S.
Quinn, Joseph
Reddy, P. Hemachandra
Publication Title: 
Arteriosclerosis, Thrombosis, and Vascular Biology

OBJECTIVE: C-Reactive protein (CRP), a cardiovascular risk marker, could also participate in atherosclerosis. Atherosclerotic plaques express CRP and interleukin (IL)-10, a major antiinflammatory cytokine. IL-10 deficiency results in increased lesion formation, whereas IL-10 delivery attenuates lesions. We tested the effect of CRP on lipopolysaccharide (LPS)-induced IL-10 secretion in human monocyte-derived macrophages (HMDMs).

Author(s): 
Singh, Uma
Devaraj, Sridevi
Dasu, Mohan R.
Ciobanu, Dana
Reusch, Jane
Jialal, Ishwarlal
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