{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T03:36:28Z","timestamp":1785814588576,"version":"3.56.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurosci"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The <jats:italic>m<\/jats:italic>-AAA (<jats:bold>A<\/jats:bold> TPases <jats:bold>A<\/jats:bold> ssociated with a variety of cellular <jats:bold>A<\/jats:bold> ctivities) is an evolutionary conserved metalloprotease complex located in the internal mitochondrial membrane. In the mouse, it is a hetero-oligomer variably formed by the <jats:italic>Spg7<\/jats:italic>, <jats:italic>Afg3l1<\/jats:italic>, and <jats:italic>Afg3l2<\/jats:italic> encoded proteins, or a homo-oligomer formed by either Afg3l1 or Afg3l2. In humans, <jats:italic>AFG3L2<\/jats:italic> and <jats:italic>SPG7<\/jats:italic> genes are conserved, whereas <jats:italic>AFG3L1<\/jats:italic> became a pseudogene. Both <jats:italic>AFG3L2<\/jats:italic> and <jats:italic>SPG7<\/jats:italic> are involved in a neurodegenerative disease, namely the autosomal dominant spinocerebellar ataxia SCA28 and a recessive form of spastic paraplegia, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Using quantitative RT-PCR, we measured the expression levels of <jats:italic>Spg7<\/jats:italic>, <jats:italic>Afg3l1<\/jats:italic>, and <jats:italic>Afg3l2<\/jats:italic> in the mouse brain. In all regions <jats:italic>Afg3l2<\/jats:italic> is the most abundant transcript, followed by <jats:italic>Spg7<\/jats:italic>, and <jats:italic>Afg3l1<\/jats:italic>, with a ratio of approximately 5:3:1 in whole-brain mRNA. Using <jats:italic>in-situ<\/jats:italic> hybridization, we showed that <jats:italic>Spg7<\/jats:italic>, <jats:italic>Afg3l1<\/jats:italic> and <jats:italic>Afg3l2<\/jats:italic> have a similar cellular pattern of expression, with high levels in mitral cells, Purkinje cells, deep cerebellar nuclei cells, neocortical and hippocampal pyramidal neurons, and brainstem motor neurons. However, in some neuronal types, differences in the level of expression of these genes were present, suggesting distinct degrees of contribution of their proteins.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Neurons involved in SCA28 and hereditary spastic paraplegia display high levels of expression, but similar or even higher expression is also present in other types of neurons, not involved in these diseases, suggesting that the selective cell sensitivity should be attributed to other, still unknown, mechanisms.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2202-11-55","type":"journal-article","created":{"date-parts":[[2010,6,2]],"date-time":"2010-06-02T18:14:18Z","timestamp":1275502458000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Mouse brain expression patterns of Spg7, Afg3l1, and Afg3l2 transcripts, encoding for the mitochondrial m-AAA protease"],"prefix":"10.1186","volume":"11","author":[{"given":"Tiziana","family":"Sacco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Boda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriola","family":"Hoxha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Pizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cagnoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Brusco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Tempia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,4,28]]},"reference":[{"key":"1614_CR1","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/S0092-8674(00)81271-4","volume":"85","author":"H Arlt","year":"1996","unstructured":"Arlt H, Tauer R, Feldmann H, Neupert W, Langer T: The YTA10-12 complex, an AAA protease with chaperone-like activity in the inner membrane of mitochondria. Cell. 1996, 85: 875-885. 10.1016\/S0092-8674(00)81271-4.","journal-title":"Cell"},{"key":"1614_CR2","doi-asserted-by":"publisher","first-page":"4837","DOI":"10.1093\/emboj\/17.16.4837","volume":"17","author":"H Arlt","year":"1998","unstructured":"Arlt H, Steglich G, Perryman R, Guiard B, Neupert W, Langer T: The formation of respiratory chain complexes in mitochondria is under the proteolytic control of the m-AAA protease. EMBO J. 1998, 17: 4837-4847. 10.1093\/emboj\/17.16.4837.","journal-title":"EMBO J"},{"key":"1614_CR3","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.cell.2005.08.003","volume":"123","author":"M Nolden","year":"2005","unstructured":"Nolden M, Ehses S, Koppen M, Bernacchia A, Rugarli EI, Langer T: The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria. Cell. 2005, 123: 277-289. 10.1016\/j.cell.2005.08.003.","journal-title":"Cell"},{"key":"1614_CR4","doi-asserted-by":"publisher","first-page":"e6975","DOI":"10.1371\/journal.pone.0006975","volume":"4","author":"T Karlberg","year":"2009","unstructured":"Karlberg T, Berg van den S, Hammarstr\u00f6m M, Sagemark J, Johansson I, Holmberg-Schiavone L, Sch\u00fcler H: Crystal structure of the ATPase domain of the human AAA+ protein paraplegin\/SPG7. PLoS One. 2009, 4: e6975-10.1371\/journal.pone.0006975.","journal-title":"PLoS One"},{"key":"1614_CR5","first-page":"211","volume-title":"Annu Rev Microbiol","author":"K Ito","year":"2005","unstructured":"Ito K, Akiyama Y: Cellular functions, mechanism of action, and regulation of FtsH protease. Annu Rev Microbiol. 2005, 211-231. 10.1146\/annurev.micro.59.030804.121316."},{"key":"1614_CR6","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/S0092-8674(00)81203-9","volume":"93","author":"G Casari","year":"1998","unstructured":"Casari G, De Fusco M, Ciarmatori S, Zeviani M, Mora M, Fernandez P, De Michele G, Filla A, Cocozza S, Marconi R, D\u00fcrr A, Fontaine B, Ballabio A: Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease. Cell. 1998, 93: 973-983. 10.1016\/S0092-8674(00)81203-9.","journal-title":"Cell"},{"key":"1614_CR7","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1136\/jnnp.69.2.150","volume":"69","author":"C McDermott","year":"2000","unstructured":"McDermott C, White K, Bushby K, Shaw P: Hereditary spastic paraparesis: a review of new developments. J Neurol Neurosurg Psychiatry. 2000, 69: 150-160. 10.1136\/jnnp.69.2.150.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1614_CR8","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/ng.544","volume":"42","author":"D Di Bella","year":"2010","unstructured":"Di Bella D, Lazzaro F, Brusco A, Plumari M, Battaglia G, Pastore A, Finardi A, Cagnoli C, Tempia F, Frontali M, Veneziano L, Sacco T, Boda E, Brussino A, Bonn F, Castellotti B, Baratta S, Mariotti C, Gellera C, Fracasso V, Magri S, Langer T, Plevani P, Di Donato S, Muzi-Falconi M, Taroni F: Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28. Nat Genet. 2010, 42: 313-331. 10.1038\/ng.544.","journal-title":"Nat Genet"},{"key":"1614_CR9","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1172\/JCI200420138","volume":"113","author":"F Ferreirinha","year":"2004","unstructured":"Ferreirinha F, Quattrini A, Pirozzi M, Valsecchi V, Dina G, Broccoli V, Auricchio A, Piemonte F, Tozzi G, Gaeta L, Casari G, Ballabio A, Rugarli EI: Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport. J Clin Invest. 2004, 113: 231-242.","journal-title":"J Clin Invest"},{"key":"1614_CR10","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1523\/JNEUROSCI.4677-07.2008","volume":"28","author":"F Maltecca","year":"2008","unstructured":"Maltecca F, Aghaie A, Schroeder DG, Cassina L, Taylor BA, Phillips SJ, Malaguti M, Previtali S, Gu\u00e9net JL, Quattrini A, Cox GA, Casari G: The mitochondrial protease AFG3L2 is essential for axonal development. J Neurosci. 2008, 28: 2827-2836. 10.1523\/JNEUROSCI.4677-07.2008.","journal-title":"J Neurosci"},{"key":"1614_CR11","doi-asserted-by":"publisher","first-page":"2001","DOI":"10.1093\/hmg\/ddp124","volume":"18","author":"P Martinelli","year":"2009","unstructured":"Martinelli P, La Mattina V, Bernacchia A, Magnoni R, Cerri F, Cox G, Quattrini A, Casari G, Rugarli EI: Genetic interaction between the m-AAA protease isoenzymes reveals novel roles in cerebellar degeneration. Hum Mol Genet. 2009, 18: 2001-2013. 10.1093\/hmg\/ddp124.","journal-title":"Hum Mol Genet"},{"key":"1614_CR12","doi-asserted-by":"publisher","first-page":"9244","DOI":"10.1523\/JNEUROSCI.1532-09.2009","volume":"29","author":"F Maltecca","year":"2009","unstructured":"Maltecca F, Magnoni R, Cerri F, Cox GA, Quattrini A, Casari G: Haploinsufficiency of AFG3L2, the gene responsible for spinocerebellar ataxia type 28, causes mitochondria-mediated Purkinje cell dark degeneration. J Neurosci. 2009, 29: 9244-9254. 10.1523\/JNEUROSCI.1532-09.2009.","journal-title":"J Neurosci"},{"key":"1614_CR13","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1083\/jcb.200304112","volume":"163","author":"L Atorino","year":"2003","unstructured":"Atorino L, Silvestri L, Koppen M, Cassina L, Ballabio A, Marconi R, Langer T, Casari G: Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia. J Cell Biol. 2003, 163: 777-787. 10.1083\/jcb.200304112.","journal-title":"J Cell Biol"},{"key":"1614_CR14","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1128\/MCB.01470-06","volume":"27","author":"M Koppen","year":"2007","unstructured":"Koppen M, Metodiev MD, Casari G, Rugarli EI, Langer T: Variable and tissue-specific subunit composition of mitochondrial m-AAA protease complexes linked to hereditary spastic paraplegia. Mol Cell Biol. 2007, 27: 758-767. 10.1128\/MCB.01470-06.","journal-title":"Mol Cell Biol"},{"key":"1614_CR15","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1007\/s12031-008-9128-9","volume":"37","author":"E Boda","year":"2009","unstructured":"Boda E, Pini A, Hoxha E, Parolisi R, Tempia F: Selection of reference genes for quantitative real time RT-PCR studies in mouse brain. J Mol Neurosci. 2009, 37: 238-253. 10.1007\/s12031-008-9128-9.","journal-title":"J Mol Neurosci"},{"key":"1614_CR16","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1046\/j.1471-4159.2000.0750383.x","volume":"75","author":"EH Pettus","year":"2000","unstructured":"Pettus EH, Betarbet R, Cottrell B, Wallace DC, Madyastha V, Greenamyre JT: Immunocytochemical characterization of the mitochondrially encoded ND1 subunit of complex I (NADH: ubiquinone oxidoreductase) in rat brain. J Neurochem. 2000, 75: 383-392. 10.1046\/j.1471-4159.2000.0750383.x.","journal-title":"J Neurochem"},{"key":"1614_CR17","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1007\/s12311-008-0053-9","volume":"7","author":"C Mariotti","year":"2008","unstructured":"Mariotti C, Brusco A, Di Bella D, Cagnoli C, Seri M, Gellera C, Di Donato S, Taroni F: Spinocerebellar ataxia type 28: A novel autosomal dominant cerebellar ataxia characterized by slow progression and ophthalmoparesis. Cerebellum. 2008, 7: 184-188. 10.1007\/s12311-008-0053-9.","journal-title":"Cerebellum"},{"key":"1614_CR18","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"G Paxinos","year":"2001","unstructured":"Paxinos G, Franklin KBJ: The Mouse Brain in Stereotaxic Coordinates. 2001, Academic Press"},{"key":"1614_CR19","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.heares.2005.10.012","volume":"211","author":"DS Bortone","year":"2006","unstructured":"Bortone DS, Mitchell K, Manis PB: Developmental time course of potassium channel expression in the rat cochlear nucleus. Hearing Research. 2006, 211: 114-125. 10.1016\/j.heares.2005.10.012.","journal-title":"Hearing Research"}],"container-title":["BMC Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2202-11-55.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T04:42:01Z","timestamp":1630471321000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurosci.biomedcentral.com\/articles\/10.1186\/1471-2202-11-55"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4,28]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["1614"],"URL":"https:\/\/doi.org\/10.1186\/1471-2202-11-55","relation":{},"ISSN":["1471-2202"],"issn-type":[{"value":"1471-2202","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,4,28]]},"assertion":[{"value":"8 July 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2010","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2010","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"55"}}