Skip to Main content Skip to Navigation
Journal articles

QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [46 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01376755
Contributor : Mireille Bos <>
Submitted on : Wednesday, October 5, 2016 - 3:32:08 PM
Last modification on : Wednesday, September 16, 2020 - 5:11:25 PM
Long-term archiving on: : Friday, January 6, 2017 - 1:52:17 PM

File

elife-17163.pdf
Publisher files allowed on an open archive

Identifiers

Citation

Virginia Guarani, Claude Jardel, Dominique Chrétien, Anne Lombès, Paule Bénit, et al.. QIL1 mutation causes MICOS disassembly and early onset fatal mitochondrial encephalopathy with liver disease. eLife, eLife Sciences Publication, 2016, ⟨10.7554/eLife.17163⟩. ⟨inserm-01376755⟩

Share

Metrics

Record views

521

Files downloads

1140