TY - JOUR
T1 - The functions of ZIP8, ZIP14, and ZnT10 in the regulation of systemic manganese homeostasis
AU - Winslow, James W.W.
AU - Limesand, Kirsten H.
AU - Zhao, Ningning
N1 - Funding Information:
Funding: This work was supported by the National Institutes of Health Grant R00DK104066 (to N.Z.).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - As an essential nutrient, manganese is required for the regulation of numerous cellular processes, including cell growth, neuronal health, immune cell function, and antioxidant defense. However, excess manganese in the body is toxic and produces symptoms of neurological and behavioral defects, clinically known as manganism. Therefore, manganese balance needs to be tightly controlled. In the past eight years, mutations of genes encoding metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism. This review focuses on the most recent advances in the understanding of physiological functions of these three identified manganese transporters and summarizes the molecular mechanisms underlying how the loss of functions in these genes leads to impaired manganese homeostasis and human diseases.
AB - As an essential nutrient, manganese is required for the regulation of numerous cellular processes, including cell growth, neuronal health, immune cell function, and antioxidant defense. However, excess manganese in the body is toxic and produces symptoms of neurological and behavioral defects, clinically known as manganism. Therefore, manganese balance needs to be tightly controlled. In the past eight years, mutations of genes encoding metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism. This review focuses on the most recent advances in the understanding of physiological functions of these three identified manganese transporters and summarizes the molecular mechanisms underlying how the loss of functions in these genes leads to impaired manganese homeostasis and human diseases.
KW - Manganese
KW - Metabolism
KW - Metal transporters
KW - ZIP14
KW - ZIP8
KW - ZnT10
UR - http://www.scopus.com/inward/record.url?scp=85084374666&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084374666&partnerID=8YFLogxK
U2 - 10.3390/ijms21093304
DO - 10.3390/ijms21093304
M3 - Review article
C2 - 32392784
AN - SCOPUS:85084374666
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 9
M1 - 3304
ER -