{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:30:44Z","timestamp":1791379844824,"version":"4.3.3"},"reference-count":70,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T00:00:00Z","timestamp":1588550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T00:00:00Z","timestamp":1588550400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alpha intercalated cells (\u03b1ICs) in the kidney collecting duct (CD) belong to a family of mitochondria rich cells (MRCs) and have a crucial role in acidifying the urine via apical V\u2010ATPase pumps. The nature of metabolism in \u03b1ICs and its relationship to transport was not well\u2010understood. Here, using multiphoton live cell imaging in mouse kidney tissue, FIB\u2010SEM, and other complementary techniques, we provide new insights into mitochondrial structure and function in \u03b1ICs. We show that \u03b1IC mitochondria have a rounded structure and are not located in close proximity to V\u2010ATPase containing vesicles. They display a bright NAD(P)H fluorescence signal and low uptake of voltage\u2010dependent dyes, but are energized by a pH gradient. However, expression of complex V (ATP synthase) is relatively low in \u03b1ICs, even when stimulated by metabolic acidosis. In contrast, anaerobic glycolytic capacity is surprisingly high, and sufficient to maintain intracellular calcium homeostasis in the presence of complete aerobic inhibition. Moreover, glycolysis is essential for V\u2010ATPase\u2010mediated proton pumping. Key findings were replicated in narrow\/clear cells in the epididymis, also part of the MRC family. In summary, using a range of cutting\u2010edge techniques to investigate \u03b1IC metabolism in situ, we have discovered that these mitochondria dense cells have a high glycolytic capacity.<\/jats:p>","DOI":"10.1096\/fj.202000273r","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T01:21:22Z","timestamp":1588641682000},"page":"8510-8525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Multiparametric imaging reveals that mitochondria\u2010rich intercalated cells in the kidney collecting duct have a very high glycolytic capacity"],"prefix":"10.1096","volume":"34","author":[{"given":"Susan","family":"Ghazi","sequence":"first","affiliation":[{"name":"Institute of Anatomy University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soline","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Institute of Physiology University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Gomariz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology University of Zurich Zurich Switzerland"},{"name":"Computer Vision Laboratory ETH Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Bugarski","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Haenni","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Zurich Zurich Switzerland"},{"name":"Center for Microscopy and Image Analysis University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana R.","family":"Martins","sequence":"additional","affiliation":[{"name":"Center for Microscopy and Image Analysis University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Nombela\u2010Arrieta","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Unwin","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine University College London  UK"},{"name":"AstraZeneca Biopharmaceuticals R&amp;D Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Physiology University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Hall","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Zurich Zurich Switzerland"},{"name":"Department of Nephrology University Hospital Zurich  Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eilidh","family":"Craigie","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.48.030186.000301"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2012.tb00420.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00044.2006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.08880914"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00045.2003"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.02014"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.028803"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017060643"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.199.11.2345"},{"key":"e_1_2_9_12_1","first-page":"F522","article-title":"Lactate production in isolated segments of the rat nephron","volume":"248","author":"Bagnasco S","year":"1985","journal-title":"Am J Physiol"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.12.7064"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008768200"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.90258.2008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00552.2009"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008070759"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(03)61019-0"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000342812"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.02.022"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/23.24.5080"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00084.2004"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000323984"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006101072"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038011"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024899"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-11-372","article-title":"Beyond co\u2010localization: inferring spatial interactions between sub\u2010cellular structures from microscopy images","volume":"11","author":"Helmuth JA","year":"2010","journal-title":"BMC Bioinform"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-04770-z","article-title":"Quantitative spatial analysis of haematopoiesis\u2010regulating stromal cells in the bone marrow microenvironment by 3D microscopy","volume":"9","author":"Gomariz A","year":"2018","journal-title":"Nat Commun"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sigpro.2009.07.009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.258.1.C171"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(92)90140-3"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.07.027"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"20250","DOI":"10.1016\/S0021-9258(17)31983-X","article-title":"Apical membrane Na+\/H+ exchange in rat medullary thick ascending limb. pH\u2010dependence and inhibition by hyperosmolality","volume":"269","author":"Watts BA","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1981.61.2.296"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00172.2005"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07518"},{"key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"C97","DOI":"10.1152\/ajpcell.00469.2003","article-title":"Glucose activates H+\u2010ATPase in kidney epithelial cells","volume":"287","author":"Nakamura S","year":"2004","journal-title":"Am J Physiol \u2010 Cell Physiol"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V72260"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1980.21"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9728.2003.00079.x"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.201110767"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114913"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221496110"},{"key":"e_1_2_9_45_1","first-page":"351","volume-title":"Methods in Molecular Biology","author":"Ramshesh VK","year":"2018"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200512100"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.008"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.12.020"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.3.F437"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.06.023"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0154371"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000255"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00076.2011"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.259.2.C286"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/6.1.52"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00754.x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00488.2009"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710964114"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar2131"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1986.66.2.469"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01870818"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65062765.x"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.10.005"},{"key":"e_1_2_9_64_1","doi-asserted-by":"crossref","first-page":"F977","DOI":"10.1152\/ajprenal.1988.255.5.F977","article-title":"Substrate specificity to maintain cellular ATP along the mouse nephron","volume":"255","author":"Uchida S","year":"1988","journal-title":"Am. J. Physiol. \u2013 Ren Physiol"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.328"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015030231"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13312"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/273947"},{"key":"e_1_2_9_69_1","first-page":"148","article-title":"Intimate association of H(+)\u2010ATPase vesicles with mitochondria in the intercalated cell of the renal collecting duct","volume":"44","author":"Yamada E","year":"1995","journal-title":"J Electron Microsc"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00561.2011"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpcy.32"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1096%2Ffj.202000273R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000273R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202000273R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202000273R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:01:45Z","timestamp":1790694105000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202000273R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,4]]},"references-count":70,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1096\/fj.202000273R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202000273r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,4]]},"assertion":[{"value":"2020-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}