Search

Salt-inducible kinase 2 (SIK2) is expressed abundantly in adipose tissues and represses cAMP-response element-binding protein (CREB)-mediated gene expression by phosphorylating the coactivator transducer of regulated CREB activity (TORC2). Phosphorylation at [Ser.sup.587] of SIK2 diminishes its TORC2 phosphorylation activity. In 3T3-LI white adipocytes, SIK2 downregulates lipogenic gene in response to nutritional stresses. To investigate the impact of SIK2 on the function of brown adipose tissue (BAT), we used T37i brown adipocytes, mice with diet-induced obesity, and SIK2 mutant (S587A) transgenic mice. When T37i adipocytes were treated with insulin, the levels of peroxisome proliferator-activated receptor-coactivator-l[alpha] (PGC-1[alpha]) and uncoupling protein-1 (UCP-1) mRNA were increased, and the induction was inhibited by overexpression of SIK2 (S587A) mutant or dominant-negative CREB. Insulin enhanced SIK2 phosphorylation at [Ser.sup.587], which was accompanied by decrease in phospho-TORC2. Similarly, the decrease in the level of SIK2 phosphorylation at [Ser.sup.587] was observed in the BAT of mice with diet-induced obesity, which was negatively correlated with TORC2 phosphorylation. To confirm the negative correlation between SIK2 phosphorylation at [Ser.sup.587] and TORC2 phosphorylation in BAT, SIK2 mutant (S587A) was overexpressed in adipose tissues by using the adipocyte fatty acid-binding protein 2 promoter. The expression of recombinant SIK2 (S587A) was restricted to BAT, and the levels of phospho-TORC2 were elevated in BAT of transgenic mice. Male transgenic mice developed high-fat diet-induced obesity, and their BAT expressed low levels of PGC-1[alpha] and UCP-1 mRNA, suggesting that SIK2-TORC2 cascade may be important for the regulation of PGC-1[alpha] and UCP-1 gene expression in insulin signaling in BAT. salt-inducible kinase 2; peroxisome proliferator-activated receptorcoactivator-l[alpha]; uncoupling protein-l; brown adipocyte; adenosine 5',3'-cyclic monophosphate-response element-binding protein

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jedc.2007.10.008 Byline: Junko Doi (a), Kazuo Mino (b) Abstract: This paper introduces consumption externalities into one of the base line models of growth in which continuing expansion of product variety sustains long-term growth. We assume that consumers set a benchmark stock of consumption for each good so that there are commodity-specific external effects. Each good is produced by a monopolistically competitive firm and the firm exploits the presence of consumption external effects in determining its profit-maximizing price. Given those settings, we show that the introduction of consumption externalities may affect the balanced-growth characterization, transitional dynamics and policy effects in fundamental manners. Author Affiliation: (a) Department of Economics, Kansai University, 3-3-35 Yamate-cho, Suita 564-8680, Japan (b) Graduate School of Economics, Osaka University, 1-7 Machikaneyama, Toyonaka, Osaka 560 0043, Japan Article History: Received 3 February 2006; Accepted 14 October 2007

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jmateco.2006.05.005 Byline: Junko Doi (a), Kazuo Nishimura (b), Koji Shimomura (c) Keywords: Endogenous growth; Externality; Stability; Trade pattern Abstract: We formulate a two-country endogenous growth model, which explain joint determination of long-run trade patterns and world growth rates. After providing the existence and local stability of the continuum of balanced growth paths, we show that main standard trade propositions hold under some modifications and that, subject to certain conditions concerning social and private rankings of factory intensities between production sectors, the higher is the growth rate, the smaller is the volume of international trade among balanced growth paths in the continuum. Author Affiliation: (a) Faculty of Economics, Kansai University, Yamate-cho, Suita, Osaka 564-8680, Japan (b) KIER, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501, Japan (c) RIEB, Kobe University, 2-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan Article History: Received 14 November 2005; Revised 18 May 2006; Accepted 27 May 2006 Article Note: (footnote) [star] We thank Christian Ghiglino, Takashi Kamihigashi and Gerhard Sorger for their useful comments on the earlier version of the paper.

This paper studies a two-sector model of endogenous technical change in which expansion of each production sector is associated with sector-specific R&D investment. It is shown that the pattern of growth is sensitive to the specification of intersectoral technological spillover as well as to the preference structure. If technological spillovers and preferences of consumers are represented by CES functional forms, the balanced-growth equilibrium may not exhibit a well-behaved saddle-point property: it is possible that the balanced-growth path is locally indeterminate or unstable. In addition, a slight modification of technological spillover effects easily yields multiple balanced-growth paths. In contrast, Cobb-Douglas specifications present a unique and determinate balanced-growth path. JEL classification: E32; O41 Keywords: Endogenous technical change; Technological spillovers; Two-sector model; Sector-specific R&D

Mitochondrial quality control, which is crucial for maintaining cellular homeostasis, has been considered to be achieved exclusively through mitophagy. Here we report an alternative mitochondrial quality control pathway mediated by extracellular mitochondria release. By performing time-lapse confocal imaging on a stable cell line with fluorescent-labeled mitochondria, we observed release of mitochondria from cells into the extracellular space. Correlative light-electron microscopy revealed that majority of the extracellular mitochondria are in free form and, on rare occasions, some are enclosed in membrane-surrounded vesicles. Rotenone- and carbonyl cyanide m-chlorophenylhydrazone-induced mitochondrial quality impairment promotes the extracellular release of depolarized mitochondria. Overexpression of PRKN (parkin RBR E3 ubiquitin protein ligase), which has a pivotal role in mitophagy regulation, suppresses the extracellular mitochondria release under basal and stress condition, whereas its knockdown exacerbates it. Correspondingly, overexpression of PRKN-independent mitophagy regulators, BNIP3 (BCL2 interacting protein 3) and BNIP3L/NIX (BCL2 interacting protein 3 like), suppress extracellular mitochondria release. Autophagy-deficient cell lines show elevated extracellular mitochondria release. These results imply that perturbation of mitophagy pathway prompts mitochondria expulsion. Presence of mitochondrial protein can also be detected in mouse sera. Sera of PRKN-deficient mice contain higher level of mitochondrial protein compared to that of wild-type mice. More importantly, fibroblasts and cerebrospinal fluid samples from Parkinson disease patients carrying loss-of-function PRKN mutations show increased extracellular mitochondria compared to control subjects, providing evidence in a clinical context. Taken together, our findings suggest that extracellular mitochondria release is a comparable yet distinct quality control pathway from conventional mitophagy. Abbreviations: ACTB: actin beta; ANXA5: annexin A5; ATP5F1A/ATP5A: ATP synthase F1 subunit alpha; ATG: autophagy related; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CM: conditioned media; CSF: cerebrospinal fluid; DMSO: dimethyl sulfoxide; EM: electron microscopy; HSPD1/Hsp60: heat shock protein family D (Hsp60) member 1; KD: knockdown; KO: knockout; MAP1LC3A/LC3: microtubule associated protein 1 light chain 3 alpha; MT-CO1: mitochondrially encoded cytochrome c oxidase I; NDUFB8: NADH:ubiquinone oxidoreductase subunit B8; OE: overexpression; OPA1: OPA1 mitochondrial dynamin like GTPase; OXPHOS: oxidative phosphorylation; PBS: phosphate-buffered saline; PB: phosphate buffer; PD: Parkinson disease; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SDHB: succinate dehydrogenase complex iron sulfur subunit B; TOMM20: translocase of outer mitochondrial membrane 20; TOMM40: translocase of outer mitochondrial membrane 40; UQCRC2: ubiquinol-cytochrome c reductase core protein 2; WT: wild-type [ABSTRACT FROM AUTHOR]