- Email: [email protected]
Inhibiting oxidative phosphorylation restrains autoimmune disease
e14
Abstracts
3. E. Forte, V.B. Borisov, M. Falabella, H.G. Colaço, M. Tinajero-Trejo, R.K. Poole, J.B. Vicente, P. Sarti, A. Giuffrè, The terminal oxidase cytochrome bd promotes sulfide-resistant bacterial respiration and growth, Sci. Rep. 6 (2016) 23788. doi:10.1016/j.bbabio.2016.04.379
Inhibiting oxidative phosphorylation restrains autoimmune disease Gary D. Glick University of Michigan Medical School, Ann Arbor MI 48109, USA E-mail address: [email protected] (G.D. Glick) Abstract not received doi:10.1016/j.bbabio.2016.04.380
Dissecting the peripheral stalk of the mitochondrial ATP synthase of chlorophycean algae Miriam Vázquez-Acevedoa, Félix Vega-deLunaa, Lorenzo SánchezVásqueza, Lilia Colina-Tenorioa, Claire Remacleb, Pierre Cardolb, Héctor Miranda-Astudillob, Diego González-Halphena, a Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico b Genetics and Physiology of Microalgae, Department of Life Sciences, University of Liège, Liège, Belgium E-mail address: [email protected] (D. González-Halphen) A highly-stable dimeric mitochondrial F1Fo-ATP synthase of 1600 kDa can be isolated from the unicellular chlorophycean algae Chlamydomonas reinhardtii and Polytomella sp. Each monomer from the ATP synthase of the colorless alga Polytomella has 17 polypeptides, eight conserved subunits [alpha, beta, gamma, delta, epsilon, a (Atp6), c (Atp9), and OSCP] and nine atypical polypeptides (Asa1 to Asa9) only present in chlorophycean algae. The Asa subunits seem to form the very robust peripheral stalk of the enzyme observed in several electron-microscope studies. We have found of interest to study the close-neighbor relationships of the ASA subunits and how they interact with the classical subunits. We have explored the topological disposition of the components of the algal mitochondrial ATP synthase with different experimental approaches: generation of sub-complexes after partial dissociation of the dimeric ATP synthase and detection of subunit–subunit interactions based on cross-linking experiments or reconstitution with recombinant subunits. Based on the obtained data and on a recent electron cryomicroscopy map of the enzyme [1], we suggest a model for the topological disposition of the subunits that constitute the algal mitochondrial ATP synthase. References 1. M. Allegretti, N. Klusch, D.J. Mills, J. Vonck, W. Kühlbrandt, K.M. Davies, Horizontal membrane-intrinsic α-helices in the stator asubunit of an F-type ATP synthase, Nature 521 (2015) 237-240. doi:10.1016/j.bbabio.2016.04.381
MTCH2: A new player in mitochondria biology Atan Gross Department of Biological Regulation, Weizmann Institute, Rehovot, Israel E-mail address: [email protected] (A. Gross)
The BCL-2 family proteins target the mitochondria to regulate apoptosis, however their mechanism of action remains poorly understood. We recently discovered that mitochondrial carrier homolog 2 (MTCH2), a novel and limitedly characterized 33 kDa mitochondrial protein is important for the mitochondrial targeting of the pro-apoptotic BCL-2 family member BID. Interestingly, MTCH2 shows some structural similarities to members of the mitochondrial carrier protein family but unlike other members of this family, which reside in the inner membrane, MTCH2 is localized to the outer membrane and thus is unlikely to act as a mitochondrial carrier. Importantly, the MTCH2 locus is associated with increased obesity in humans, and we recently showed that muscle MTCH2 deficiency in mice provides protection from a highfat diet [1]. Moreover, we demonstrated that loss of muscle MTCH2 triggers increased muscle metabolism, elevated whole-body energy demand and heat production, which possibly explains the protection from diet-induced obesity. In addition, metabolic profiling of mice deficient in muscle MTCH2 revealed a profile that resembles the profile observed in starved mice, suggesting that MTCH2 acts as a repressor of “starved state” metabolism. We are now at the stage of using these clues and additional approaches to determine MTCH2's mechanism of action, and its role in apoptosis regulated by BCL-2 family proteins.
References 1. L. Buzaglo-Azriel, Y. Kuperman, M. Tsoory, Y. Zaltsman, L. Shachnai, S.L. Zaidman, E. Bassat, I. Michailovici, A. Sarver, E. Tzahor, M. Haran, C. Vernochet, A. Gross, Loss of muscle MTCH2 increases whole-body energy utilization and protects from diet-induced obesity. Cell Reports 14 (2016) 1602–1610.
doi:10.1016/j.bbabio.2016.04.382
Dependence of mitochondrial Ca2+ uptake on the molecular composition of the uniporter György Hajnóczky, Melanie Paillard, György Csordás, Valentina Debattisti, Ádám Bartók, Cynthia Moffat, Erin L. Seifert MitoCare Center, Thomas Jefferson University, Philadelphia, PA, USA E-mail address: [email protected] (G. Hajnóczky) A central paradigm of mitochondrial research is the decoding of cytoplasmic calcium signals by the mitochondria to adjust oxidative metabolism to the energy needs of the cell. Calcium signals and energy demands are tissue specific raising the fundamental question how mitochondria adapted to the diverse needs. Previous results have indicated that mitochondrial calcium uptake shows varying activities in different tissues and the recent molecular definition of the mitochondrial calcium uniporter made possible to test the idea that the uniporter components display tissue-specific differences to create tissue-specific mitochondrial calcium handling phenotypes. In the present work, we demonstrate that the striking differences in mitochondrial calcium phenotypes (threshold and cooperativity) of cardiac muscle, skeletal muscle and liver are aligned with their relative abundance of the uniporter's pore forming protein. MCU and its calcium sensors, MICU1/2/3. Furthermore, we succeeded with reprogramming of cardiac mitochondria to liver phenotype and vice versa with altering MICU relative to MCU.
doi:10.1016/j.bbabio.2016.04.383
Abstracts
3. E. Forte, V.B. Borisov, M. Falabella, H.G. Colaço, M. Tinajero-Trejo, R.K. Poole, J.B. Vicente, P. Sarti, A. Giuffrè, The terminal oxidase cytochrome bd promotes sulfide-resistant bacterial respiration and growth, Sci. Rep. 6 (2016) 23788. doi:10.1016/j.bbabio.2016.04.379
Inhibiting oxidative phosphorylation restrains autoimmune disease Gary D. Glick University of Michigan Medical School, Ann Arbor MI 48109, USA E-mail address: [email protected] (G.D. Glick) Abstract not received doi:10.1016/j.bbabio.2016.04.380
Dissecting the peripheral stalk of the mitochondrial ATP synthase of chlorophycean algae Miriam Vázquez-Acevedoa, Félix Vega-deLunaa, Lorenzo SánchezVásqueza, Lilia Colina-Tenorioa, Claire Remacleb, Pierre Cardolb, Héctor Miranda-Astudillob, Diego González-Halphena, a Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico b Genetics and Physiology of Microalgae, Department of Life Sciences, University of Liège, Liège, Belgium E-mail address: [email protected] (D. González-Halphen) A highly-stable dimeric mitochondrial F1Fo-ATP synthase of 1600 kDa can be isolated from the unicellular chlorophycean algae Chlamydomonas reinhardtii and Polytomella sp. Each monomer from the ATP synthase of the colorless alga Polytomella has 17 polypeptides, eight conserved subunits [alpha, beta, gamma, delta, epsilon, a (Atp6), c (Atp9), and OSCP] and nine atypical polypeptides (Asa1 to Asa9) only present in chlorophycean algae. The Asa subunits seem to form the very robust peripheral stalk of the enzyme observed in several electron-microscope studies. We have found of interest to study the close-neighbor relationships of the ASA subunits and how they interact with the classical subunits. We have explored the topological disposition of the components of the algal mitochondrial ATP synthase with different experimental approaches: generation of sub-complexes after partial dissociation of the dimeric ATP synthase and detection of subunit–subunit interactions based on cross-linking experiments or reconstitution with recombinant subunits. Based on the obtained data and on a recent electron cryomicroscopy map of the enzyme [1], we suggest a model for the topological disposition of the subunits that constitute the algal mitochondrial ATP synthase. References 1. M. Allegretti, N. Klusch, D.J. Mills, J. Vonck, W. Kühlbrandt, K.M. Davies, Horizontal membrane-intrinsic α-helices in the stator asubunit of an F-type ATP synthase, Nature 521 (2015) 237-240. doi:10.1016/j.bbabio.2016.04.381
MTCH2: A new player in mitochondria biology Atan Gross Department of Biological Regulation, Weizmann Institute, Rehovot, Israel E-mail address: [email protected] (A. Gross)
The BCL-2 family proteins target the mitochondria to regulate apoptosis, however their mechanism of action remains poorly understood. We recently discovered that mitochondrial carrier homolog 2 (MTCH2), a novel and limitedly characterized 33 kDa mitochondrial protein is important for the mitochondrial targeting of the pro-apoptotic BCL-2 family member BID. Interestingly, MTCH2 shows some structural similarities to members of the mitochondrial carrier protein family but unlike other members of this family, which reside in the inner membrane, MTCH2 is localized to the outer membrane and thus is unlikely to act as a mitochondrial carrier. Importantly, the MTCH2 locus is associated with increased obesity in humans, and we recently showed that muscle MTCH2 deficiency in mice provides protection from a highfat diet [1]. Moreover, we demonstrated that loss of muscle MTCH2 triggers increased muscle metabolism, elevated whole-body energy demand and heat production, which possibly explains the protection from diet-induced obesity. In addition, metabolic profiling of mice deficient in muscle MTCH2 revealed a profile that resembles the profile observed in starved mice, suggesting that MTCH2 acts as a repressor of “starved state” metabolism. We are now at the stage of using these clues and additional approaches to determine MTCH2's mechanism of action, and its role in apoptosis regulated by BCL-2 family proteins.
References 1. L. Buzaglo-Azriel, Y. Kuperman, M. Tsoory, Y. Zaltsman, L. Shachnai, S.L. Zaidman, E. Bassat, I. Michailovici, A. Sarver, E. Tzahor, M. Haran, C. Vernochet, A. Gross, Loss of muscle MTCH2 increases whole-body energy utilization and protects from diet-induced obesity. Cell Reports 14 (2016) 1602–1610.
doi:10.1016/j.bbabio.2016.04.382
Dependence of mitochondrial Ca2+ uptake on the molecular composition of the uniporter György Hajnóczky, Melanie Paillard, György Csordás, Valentina Debattisti, Ádám Bartók, Cynthia Moffat, Erin L. Seifert MitoCare Center, Thomas Jefferson University, Philadelphia, PA, USA E-mail address: [email protected] (G. Hajnóczky) A central paradigm of mitochondrial research is the decoding of cytoplasmic calcium signals by the mitochondria to adjust oxidative metabolism to the energy needs of the cell. Calcium signals and energy demands are tissue specific raising the fundamental question how mitochondria adapted to the diverse needs. Previous results have indicated that mitochondrial calcium uptake shows varying activities in different tissues and the recent molecular definition of the mitochondrial calcium uniporter made possible to test the idea that the uniporter components display tissue-specific differences to create tissue-specific mitochondrial calcium handling phenotypes. In the present work, we demonstrate that the striking differences in mitochondrial calcium phenotypes (threshold and cooperativity) of cardiac muscle, skeletal muscle and liver are aligned with their relative abundance of the uniporter's pore forming protein. MCU and its calcium sensors, MICU1/2/3. Furthermore, we succeeded with reprogramming of cardiac mitochondria to liver phenotype and vice versa with altering MICU relative to MCU.
doi:10.1016/j.bbabio.2016.04.383