TY - JOUR
T1 - Multifaceted Roles of AFG3L2, a Mitochondrial ATPase in Relation to Neurological Disorders
AU - Ghosh Dastidar, Ranita
AU - Banerjee, Saradindu
AU - Lal, Piyush Behari
AU - Ghosh Dastidar, Somasish
N1 - Publisher Copyright:
© The Author(s) 2023.
PY - 2024/7
Y1 - 2024/7
N2 - AFG3L2 is a zinc metalloprotease and an ATPase localized in an inner mitochondrial membrane involved in mitochondrial quality control of several nuclear- and mitochondrial-encoded proteins. Mutations in AFG3L2 lead to diseases like slow progressive ataxia, which is a neurological disorder. This review delineates the cellular functions of AFG3L2 and its dysfunction that leads to major clinical outcomes, which include spinocerebellar ataxia type 28, spastic ataxia type 5, and optic atrophy type 12. It summarizes all relevant AFG3L2 mutations associated with the clinical outcomes to understand the detailed mechanisms attributable to its structure-related multifaceted roles in proteostasis and quality control. We face early diagnostic challenges of ataxia and optic neuropathy due to asymptomatic parents and variable clinical manifestations due to heterozygosity/homozygosity of AFG3L2 mutations. This review intends to promote AFG3L2 as a putative prognostic or diagnostic marker. Graphical Abstract: Functions, mutations, and clinical manifestations in AFG3L2, a mitochondrial AAA + ATPases. (Figure presented.)
AB - AFG3L2 is a zinc metalloprotease and an ATPase localized in an inner mitochondrial membrane involved in mitochondrial quality control of several nuclear- and mitochondrial-encoded proteins. Mutations in AFG3L2 lead to diseases like slow progressive ataxia, which is a neurological disorder. This review delineates the cellular functions of AFG3L2 and its dysfunction that leads to major clinical outcomes, which include spinocerebellar ataxia type 28, spastic ataxia type 5, and optic atrophy type 12. It summarizes all relevant AFG3L2 mutations associated with the clinical outcomes to understand the detailed mechanisms attributable to its structure-related multifaceted roles in proteostasis and quality control. We face early diagnostic challenges of ataxia and optic neuropathy due to asymptomatic parents and variable clinical manifestations due to heterozygosity/homozygosity of AFG3L2 mutations. This review intends to promote AFG3L2 as a putative prognostic or diagnostic marker. Graphical Abstract: Functions, mutations, and clinical manifestations in AFG3L2, a mitochondrial AAA + ATPases. (Figure presented.)
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U2 - 10.1007/s12035-023-03768-z
DO - 10.1007/s12035-023-03768-z
M3 - Review article
C2 - 38012514
AN - SCOPUS:85178134469
SN - 0893-7648
VL - 61
SP - 3788
EP - 3808
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 7
ER -