In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-09-13)
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.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.17163.001
DOI:
10.7554/eLife.17163.002
DOI:
10.7554/eLife.17163.003
DOI:
10.7554/eLife.17163.004
DOI:
10.7554/eLife.17163.005
DOI:
10.7554/eLife.17163.006
DOI:
10.7554/eLife.17163.007
DOI:
10.7554/eLife.17163.008
DOI:
10.7554/eLife.17163.009
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
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