QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease
Previously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (Guarani et al., 2015). Here, we identify QIL1 null alleles in two si...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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eLife Sciences Publications Ltd
2016-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/17163 |
| _version_ | 1811181049900695552 |
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| author | Virginia Guarani Claude Jardel Dominique Chrétien Anne Lombès Paule Bénit Clémence Labasse Emmanuelle Lacène Agnès Bourillon Apolline Imbard Jean-François Benoist Imen Dorboz Mylène Gilleron Eric S Goetzman Pauline Gaignard Abdelhamid Slama Monique Elmaleh-Bergès Norma B Romero Pierre Rustin Hélène Ogier de Baulny Joao A Paulo J Wade Harper Manuel Schiff |
| author_facet | Virginia Guarani Claude Jardel Dominique Chrétien Anne Lombès Paule Bénit Clémence Labasse Emmanuelle Lacène Agnès Bourillon Apolline Imbard Jean-François Benoist Imen Dorboz Mylène Gilleron Eric S Goetzman Pauline Gaignard Abdelhamid Slama Monique Elmaleh-Bergès Norma B Romero Pierre Rustin Hélène Ogier de Baulny Joao A Paulo J Wade Harper Manuel Schiff |
| author_sort | Virginia Guarani |
| collection | DOAJ |
| description | Previously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy with liver disease, including defects in respiratory chain function in patient muscle. QIL1 absence in patients’ fibroblasts was associated with MICOS disassembly, abnormal cristae, mild cytochrome c oxidase defect, and sensitivity to glucose withdrawal. QIL1 expression rescued cristae defects, and promoted re-accumulation of MICOS subunits to facilitate MICOS assembly. MICOS assembly and cristae morphology were not efficiently rescued by over-expression of other MICOS subunits in patient fibroblasts. Taken together, these data provide the first evidence of altered MICOS assembly linked with a human mitochondrial disease and confirm a central role for QIL1 in stable MICOS complex formation. |
| first_indexed | 2024-04-11T09:13:07Z |
| format | Article |
| id | doaj.art-c2eb5d8eb5b14293a741ed6e1db3525a |
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| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:13:07Z |
| publishDate | 2016-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c2eb5d8eb5b14293a741ed6e1db3525a2022-12-22T04:32:28ZengeLife Sciences Publications LtdeLife2050-084X2016-09-01510.7554/eLife.17163QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver diseaseVirginia Guarani0Claude Jardel1Dominique Chrétien2Anne Lombès3Paule Bénit4Clémence Labasse5Emmanuelle Lacène6Agnès Bourillon7Apolline Imbard8Jean-François Benoist9Imen Dorboz10Mylène Gilleron11Eric S Goetzman12Pauline Gaignard13Abdelhamid Slama14Monique Elmaleh-Bergès15Norma B Romero16Pierre Rustin17Hélène Ogier de Baulny18Joao A Paulo19J Wade Harper20https://orcid.org/0000-0002-6944-7236Manuel Schiff21Department of Cell Biology, Harvard Medical School, Boston, United StatesInserm U1016, Institut Cochin, CNRS UMR 8104, Paris, France; Department of Biochemistry, APHP, GHU Pitié-Salpêtrière, Paris, France; Université Paris-Descartes, Paris, FranceUMR1141, PROTECT, INSERM, Université Paris-Diderot, Sorbonne Paris Cité, Paris, FranceInserm U1016, Institut Cochin, CNRS UMR 8104, Paris, France; Department of Biochemistry, APHP, GHU Pitié-Salpêtrière, Paris, France; Université Paris-Descartes, Paris, FranceUMR1141, PROTECT, INSERM, Université Paris-Diderot, Sorbonne Paris Cité, Paris, FranceNeuromuscular morphology unit, Institut de Myologie, GHU Pitié-Salpêtrière, APHP, Paris, FranceNeuromuscular morphology unit, Institut de Myologie, GHU Pitié-Salpêtrière, APHP, Paris, FranceDepartment of Biochemistry, Hôpital Robert Debré, APHP, Paris, FranceDepartment of Biochemistry, Hôpital Robert Debré, APHP, Paris, FranceDepartment of Biochemistry, Hôpital Robert Debré, APHP, Paris, FranceUMR1141, PROTECT, INSERM, Université Paris-Diderot, Sorbonne Paris Cité, Paris, FranceInserm U1016, Institut Cochin, CNRS UMR 8104, Paris, France; Department of Biochemistry, APHP, GHU Pitié-Salpêtrière, Paris, France; Université Paris-Descartes, Paris, FranceDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, United States; University of Pittsburgh, Pittsburgh, United States; Children's Hospital of Pittsburgh of UPMC, Pittsburgh, United StatesDepartment of Biochemistry, Hôpital Bicêtre, APHP, Paris, FranceDepartment of Biochemistry, Hôpital Bicêtre, APHP, Paris, FranceDepartment of Radiology, Hôpital Robert Debré, APHP, Paris, FranceNeuromuscular morphology unit, Institut de Myologie, GHU Pitié-Salpêtrière, APHP, Paris, FranceUMR1141, PROTECT, INSERM, Université Paris-Diderot, Sorbonne Paris Cité, Paris, FranceReference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, FranceDepartment of Cell Biology, Harvard Medical School, Boston, United StatesDepartment of Cell Biology, Harvard Medical School, Boston, United StatesUMR1141, PROTECT, INSERM, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France; Reference Center for Inborn Errors of Metabolism, Robert Debré University Hospital, APHP, Paris, FrancePreviously, we identified QIL1 as a subunit of mitochondrial contact site (MICOS) complex and demonstrated a role for QIL1 in MICOS assembly, mitochondrial respiration, and cristae formation critical for mitochondrial architecture (Guarani et al., 2015). Here, we identify QIL1 null alleles in two siblings displaying multiple clinical symptoms of early-onset fatal mitochondrial encephalopathy with liver disease, including defects in respiratory chain function in patient muscle. QIL1 absence in patients’ fibroblasts was associated with MICOS disassembly, abnormal cristae, mild cytochrome c oxidase defect, and sensitivity to glucose withdrawal. QIL1 expression rescued cristae defects, and promoted re-accumulation of MICOS subunits to facilitate MICOS assembly. MICOS assembly and cristae morphology were not efficiently rescued by over-expression of other MICOS subunits in patient fibroblasts. Taken together, these data provide the first evidence of altered MICOS assembly linked with a human mitochondrial disease and confirm a central role for QIL1 in stable MICOS complex formation.https://elifesciences.org/articles/17163QIL1MICOSmitochondrial diseaseearly-onset fatal mitochondrial encephalopathy3-methylglutaconic acidurialiver disease |
| spellingShingle | Virginia Guarani Claude Jardel Dominique Chrétien Anne Lombès Paule Bénit Clémence Labasse Emmanuelle Lacène Agnès Bourillon Apolline Imbard Jean-François Benoist Imen Dorboz Mylène Gilleron Eric S Goetzman Pauline Gaignard Abdelhamid Slama Monique Elmaleh-Bergès Norma B Romero Pierre Rustin Hélène Ogier de Baulny Joao A Paulo J Wade Harper Manuel Schiff QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease eLife QIL1 MICOS mitochondrial disease early-onset fatal mitochondrial encephalopathy 3-methylglutaconic aciduria liver disease |
| title | QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease |
| title_full | QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease |
| title_fullStr | QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease |
| title_full_unstemmed | QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease |
| title_short | QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease |
| title_sort | qil1 mutation causes micos disassembly and early onset fatal mitochondrial encephalopathy with liver disease |
| topic | QIL1 MICOS mitochondrial disease early-onset fatal mitochondrial encephalopathy 3-methylglutaconic aciduria liver disease |
| url | https://elifesciences.org/articles/17163 |
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