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Publication
Kidney epithelial targeted mitochondrial transcription factor A deficiency
results in progressive mitochondrial depletion associated with severe cystic
disease.
Authors Ishii K, Kobayashi H, Taguchi K, Guan N, Li A, Tong C, Davidoff O, Tran PV,
Sharma M, Chandel NS, Kapp ME, Fogo AB, Brooks CR, Haase VH
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Kidney international
Year 2021
Date Published 3/1/2021
Volume : Pages 99 : 657 - 670
PubMed Reference 33159962
Abstract Abnormal mitochondrial function is a well-recognized feature of acute and
chronic kidney diseases. To gain insight into the role of mitochondria in kidney
homeostasis and pathogenesis, we targeted mitochondrial transcription factor A
(TFAM), a protein required for mitochondrial DNA replication and transcription
that plays a critical part in the maintenance of mitochondrial mass and
function. To examine the consequences of disrupted mitochondrial function in
kidney epithelial cells, we inactivated TFAM in sine oculis-related homeobox
2-expressing kidney progenitor cells. TFAM deficiency resulted in significantly
decreased mitochondrial gene expression, mitochondrial depletion, inhibition of
nephron maturation and the development of severe postnatal cystic disease, which
resulted in premature death. This was associated with abnormal mitochondrial
morphology, a reduction in oxygen consumption and increased glycolytic flux.
Furthermore, we found that TFAM expression was reduced in murine and human
polycystic kidneys, which was accompanied by mitochondrial depletion. Thus, our
data suggest that dysregulation of TFAM expression and mitochondrial depletion
are molecular features of kidney cystic disease that may contribute to its
pathogenesis.




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