Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis

Centrosomes are major microtubule-organizing centers of animal cells that consist of two centrioles. In mitotic cells, centrosomes are duplicated to serve as the poles of the mitotic spindle, while in quiescent cells, centrosomes move to the apical membrane where the oldest centriole is transformed...

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Main Authors: Shubhra Majumder, Ayla Cash, Harold A. Fisk
Format: Article
Language:English
Published: MDPI AG 2015-07-01
Series:Cells
Subjects:
Online Access:http://www.mdpi.com/2073-4409/4/3/331
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author Shubhra Majumder
Ayla Cash
Harold A. Fisk
author_facet Shubhra Majumder
Ayla Cash
Harold A. Fisk
author_sort Shubhra Majumder
collection DOAJ
description Centrosomes are major microtubule-organizing centers of animal cells that consist of two centrioles. In mitotic cells, centrosomes are duplicated to serve as the poles of the mitotic spindle, while in quiescent cells, centrosomes move to the apical membrane where the oldest centriole is transformed into a basal body to assemble a primary cilium. We recently showed that mitochondrial outer membrane porin VDAC3 localizes to centrosomes where it negatively regulates ciliogenesis. We show here that the other two family members, VDAC1 and VDAC2, best known for their function in mitochondrial bioenergetics, are also found at centrosomes. Like VDAC3, centrosomal VDAC1 is predominantly localized to the mother centriole, while VDAC2 localizes to centriolar satellites in a microtubule-dependent manner. Down-regulation of VDAC1 leads to inappropriate ciliogenesis, while its overexpression suppresses cilia formation, suggesting that VDAC1 and VDAC3 both negatively regulate ciliogenesis. However, this negative effect on ciliogenesis is not shared by VDAC2, which instead appears to promote maturation of primary cilia. Moreover, because overexpression of VDAC3 cannot compensate for depletion of VDAC1, our data suggest that while the entire VDAC family localizes to centrosomes, they have non-redundant functions in cilogenesis.
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spelling doaj.art-eb4a1791efa74854bee197290835a8842023-09-03T04:07:13ZengMDPI AGCells2073-44092015-07-014333135310.3390/cells4030331cells4030331Non-Overlapping Distributions and Functions of the VDAC Family in CiliogenesisShubhra Majumder0Ayla Cash1Harold A. Fisk2Department of Molecular Genetics, The Ohio State University, 484 W. 12th Avenue, Columbus, OH 43210-1292, USADepartment of Molecular Genetics, The Ohio State University, 484 W. 12th Avenue, Columbus, OH 43210-1292, USADepartment of Molecular Genetics, The Ohio State University, 484 W. 12th Avenue, Columbus, OH 43210-1292, USACentrosomes are major microtubule-organizing centers of animal cells that consist of two centrioles. In mitotic cells, centrosomes are duplicated to serve as the poles of the mitotic spindle, while in quiescent cells, centrosomes move to the apical membrane where the oldest centriole is transformed into a basal body to assemble a primary cilium. We recently showed that mitochondrial outer membrane porin VDAC3 localizes to centrosomes where it negatively regulates ciliogenesis. We show here that the other two family members, VDAC1 and VDAC2, best known for their function in mitochondrial bioenergetics, are also found at centrosomes. Like VDAC3, centrosomal VDAC1 is predominantly localized to the mother centriole, while VDAC2 localizes to centriolar satellites in a microtubule-dependent manner. Down-regulation of VDAC1 leads to inappropriate ciliogenesis, while its overexpression suppresses cilia formation, suggesting that VDAC1 and VDAC3 both negatively regulate ciliogenesis. However, this negative effect on ciliogenesis is not shared by VDAC2, which instead appears to promote maturation of primary cilia. Moreover, because overexpression of VDAC3 cannot compensate for depletion of VDAC1, our data suggest that while the entire VDAC family localizes to centrosomes, they have non-redundant functions in cilogenesis.http://www.mdpi.com/2073-4409/4/3/331centrosomeciliaciliogenesisVDACmitochondria
spellingShingle Shubhra Majumder
Ayla Cash
Harold A. Fisk
Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis
Cells
centrosome
cilia
ciliogenesis
VDAC
mitochondria
title Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis
title_full Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis
title_fullStr Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis
title_full_unstemmed Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis
title_short Non-Overlapping Distributions and Functions of the VDAC Family in Ciliogenesis
title_sort non overlapping distributions and functions of the vdac family in ciliogenesis
topic centrosome
cilia
ciliogenesis
VDAC
mitochondria
url http://www.mdpi.com/2073-4409/4/3/331
work_keys_str_mv AT shubhramajumder nonoverlappingdistributionsandfunctionsofthevdacfamilyinciliogenesis
AT aylacash nonoverlappingdistributionsandfunctionsofthevdacfamilyinciliogenesis
AT haroldafisk nonoverlappingdistributionsandfunctionsofthevdacfamilyinciliogenesis