Aging (senescence) is characterized by the development of numerous pathologies, some of which limit lifespan. Key to understanding aging is discovery of the mechanisms (etiologies) that cause senescent pathology. In C. elegans, a major senescent pathology of unknown etiology is atrophy of its principal metabolic organ, the intestine. Here we identify a cause of not only this pathology but also of yolky lipid accumulation and redistribution (a form of senescent obesity): autophagy-mediated conversion of intestinal biomass into yolk. Inhibiting intestinal autophagy or vitellogenesis rescues both visceral pathologies and can also extend lifespan. This defines a disease syndrome leading to multimorbidity and contributing to late-life mortality. Activation of gut-to-yolk biomass conversion by insulin/IGF-1 signaling (IIS) promotes reproduction and senescence. This illustrates how major, IIS-promoted senescent pathologies in C. elegans can originate not from damage accumulation but from direct effects of futile, continued action of a wild-type biological program (vitellogenesis).
Photoactive preparations were obtained by treatment of photosynthetic membranes with lipid micelles and deoxycholate.A photosystem I preparation can be extracted from the membranes by both lipid micelles and deoxycholate, whereas the photosystem II preparation remains in a particulate state.The photosystem II preparation exhibits electron transfer activity measured by photoreduction of 2,6-dichlorophenolindophenol with 1,5-diphenylcarbazide as an electron donor and has a ratio of chlorophyll a/b of 1.4. This preparation contains three major polypeptides of cytoplasmic origin and two of chloroplastic origin.The photosystem I preparation exhibits high rates of methylviologen photoreduction with ascorbate and 2,6-dichlorophenolindophenol as electron donors and does not contain chlorophyll b. This preparation contains two major polypeptides of chloroplastic origin and one of cytoplasmic origin. These results indicate that both cytoplasm and chloroplast contribute polypeptides for the formation of photosystems I and II in Chlamydomonas reinhardi.
Abstract In 38C B lymphocytes the membrane form of IgM is displayed on the cell surface whereas the secretory form of IgM is degraded. In the EH cell line, a light chain-deficient variant of 38C cells, the mu heavy chains are partially assembled with surrogate light chains characteristic of pre-B cells. In these cells neither the membrane (microns) nor the secretory (microsecond) forms of the mu heavy chain reach their final destination, and both are rapidly degraded. The degradation of mu chains in EH cells, like that of microsecond in 38C cells, is nonlysosomal and occurs prior to the trans-Golgi. However, while microsecond degradation in 38C cells is inhibited by brefeldin A, in EH cells microsecond and micron are retained and degraded by a brefeldin A-insensitive mechanism. These results indicate that degradation in EH cells occurs within the endoplasmic reticulum, whereas degradation in 38C cells requires exit from this compartment. Thus, mu heavy chains can be degraded in multiple sites along the secretory pathway. The location of the degradation process is determined by the developmentally regulated assembly species of the mu chains with either classical or surrogate light chains.
Conformation, structure, and oligomeric state of immunoglobulins not only control quality and functional properties of antibodies but are also critical for immunoglobulins secretion. Unassembled immunoglobulin heavy chains are retained intracellularly by delayed folding of the C(H)1 domain and irreversible interaction of BiP with this domain. Here we show that the three C(H)1 cysteines play a central role in immunoglobulin folding, assembly, and secretion. Remarkably, ablating all three C(H)1 cysteines negates retention and enables BiP cycling and non-canonical folding and assembly. This phenomenon is explained by interdependent formation of intradomain and interchain disulfides, although both bonds are dispensable for secretion. Substituting Cys-195 prevents formation not only of the intradomain disulfide, but also of the interchain disulfide bond with light chain, BiP displacement, and secretion. Mutating the light chain-interacting Cys-128 hinders disulfide bonding of intradomain cysteines, allowing their opportunistic bonding with light chain, without hampering secretion. We propose that the role of C(H)1 cysteines in immunoglobulin assembly and secretion is not simply to engage in disulfide bridges, but to direct proper folding and interact with the retention machinery.
Aging (senescence) is characterized by the development of numerous pathologies, some of which limit lifespan. Key to understanding aging is discovery of the mechanisms (etiologies) that cause senescent pathology. In Caenorhabditis elegans a major senescent pathology of unknown etiology is atrophy of its principal metabolic organ, the intestine. Here we identify a cause of not only this pathology, but also of yolky lipid accumulation and redistribution (a form of senescent obesity): autophagy-mediated conversion of intestinal biomass into yolk. Inhibiting intestinal autophagy or vitellogenesis rescues both visceral pathologies, and can also extend lifespan. This defines a disease syndrome leading to polymorbidity and contributing to late-life mortality. Activation of gut-to-yolk biomass conversion by insulin/IGF-1 signaling (IIS) promotes reproduction and senescence. This illustrates how major, IIS-promoted senescent pathologies in C. elegans can originate not from damage accumulation, but from continued action of a wild-type function (vitellogenesis), consistent with the recently proposed hyperfunction theory of aging.
In macroautophagy, membrane structures called autophagosomes engulf substrates and deliver them for lysosomal degradation. Autophagosomes enwrap a variety of targets with diverse sizes, from portions of cytosol to larger organelles. However, the mechanism by which autophagosome size is controlled remains elusive. We characterized a novel ER membrane protein, ERdj8, in mammalian cells. ERdj8 localizes to a meshwork-like ER subdomain along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins. ERdj8 overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8 ablation resulted in a defect in engulfing larger targets. C. elegans, in which the ERdj8 orthologue dnj-8 was knocked down, could perform autophagy on smaller mitochondria derived from the paternal lineage but not the somatic mitochondria. Thus, ERdj8 may play a critical role in autophagosome formation by providing the capacity to target substrates of diverse sizes for degradation.
Journal Article Precursor of Rat Liver α2u-Globulin: Partial Amino Acid Sequence Determination of Its Signal Peptide Get access Yukio IKEHARA, Yukio IKEHARA *Department of Biochemistry, Fukuoka University School of MedicineNanakuma, Nishi-ku, Fukuoka, Fukuoka 814-01 Search for other works by this author on: Oxford Academic PubMed Google Scholar Kimimitsu ODA, Kimimitsu ODA *Department of Biochemistry, Fukuoka University School of MedicineNanakuma, Nishi-ku, Fukuoka, Fukuoka 814-01 Search for other works by this author on: Oxford Academic PubMed Google Scholar Melvin G. ROSENFELD, Melvin G. ROSENFELD **Department of Cell Biology, New York University School of MedicineNew York, N.Y. 10016, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Shoshana BAR-NUN, Shoshana BAR-NUN **Department of Cell Biology, New York University School of MedicineNew York, N.Y. 10016, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gert KREIBICH Gert KREIBICH **Department of Cell Biology, New York University School of MedicineNew York, N.Y. 10016, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 90, Issue 6, October 1981, Pages 1833–1836, https://doi.org/10.1093/oxfordjournals.jbchem.a133664 Published: 01 October 1981 Article history Received: 21 September 1981 Published: 01 October 1981
