MITF-M binds the promoters of v-ATPase target genes

Stable Identifier
R-HSA-9858883
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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MITF-M binds the promoters of v-ATPase target genes
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The v-ATPase is an evolutionarily conserved complex, closely related to the mitochondrial ATP synthase, that consists of 14 subunits organized in two domains. The transmembrane V0 domain forms a pore to allow passage of protons through the membrane while the cytosolic V1 domain uses the energy from ATP hydrolysis to pump protons through the pore (Merkulova et al, 2015; Rujano et al, 2017; reviewed in Eaton et al, 2021). Based on ChIP studies in Drosophila gut cells and human melanoma and melanocyte cells, MITF binds to M-box elements in the promoters of all 14 genes encoding the v-ATPase proteins, as well as to the promoter of the ATP6AP2 gene, encoding an accessory protein required for the assembly and function of the v-ATPase (Zhang et al, 2015; reviewed in Eaton et al, 2021). 10 of these 15 genes show downregulation of expression upon treatment with siRNA against MITF in human melanoma cells (Zhang et al, 2015; Bouche et al, 2016). The v-ATPase complex regulates acidification of organelles including the lysosome and additionally regulates the activation of TORC1 (target of rapamcyin complex 1) in response to amino-acid levels. MITF-dependent regulation of the v-ATPase and, indirectly, of TORC1 activity may contribute to integration of response to nutrients and autophagy (reviewed in Goding and Arnheiter, 2019).
The relationship of MITF family members and TORC1 is not entirely clear. MITF family members have been implicated in both positive and negative regulation of TORC1 activity (reviewed in Martina et al, 2014). TORC1 has also been shown to regulate the nuclear/cytoplasmic ratio of MITF family members through the RAG-mediated recruitment to the lysosome and subsequent TORC1-dependent phosphorylation; MITF-M, however, does not share the conserved N-terminal region that is required for the interaction with RAG GTPases (Martina and Puertollano et al, 2013). Finally, TORC1 has also been shown to be a negative regulator of MITF activity, as TORC1 inhibition results in upregulation of MITF and melanogenic enzymes, an increase in melanin production and melanogenesis (Hah et al, 2012; Ho et al, 2011; reviewed in Martina et al, 2014; Goding and Arnheiter, 2019)
Literature References
PubMed ID Title Journal Year
26442671 Mapping the H(+) (V)-ATPase interactome: identification of proteins involved in trafficking, folding, assembly and phosphorylation

Marshansky, V, Azroyan, A, Păunescu, TG, Breton, S, Merkulova, M, Brown, D

Sci Rep 2015
26092939 Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1

Hsing, M, Siddaway, R, Goding, CR, Zhou, Q, Zhang, T, Pignoni, F, Ogmundsdottir, MH, Palsson, A, Steingrímsson, E, Möller, K, Kong, SW, Larue, L

J Cell Sci 2015
33326313 The H+-ATPase (V-ATPase): from proton pump to signaling complex in health and disease

Eaton, AF, Merkulova, M, Brown, D

Am J Physiol Cell Physiol 2021
22577264 Induction of melanogenesis by rapamycin in human MNT-1 melanoma cells

Kim, CY, Cho, HY, Kim, JG, Hah, YS, Lim, TY, Yoon, TJ, Park, DH, Yoon, J, Kim, HM

Ann Dermatol 2012
29127204 Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects

Panasyuk, G, Wada, Y, Reunert, J, Schwake, M, Bird, TD, Guida, MC, Matthijs, G, Krogan, NJ, Péanne, R, Park, JH, Hauser, V, Kretz, O, Nobre, S, Foulquier, F, Rujano, MA, Duvet, S, Garcia, P, Quelhas, D, Cannata Serio, M, Souche, E, Raskind, WH, Freisinger, P, Jager, S, Marquardt, T, Rymen, D, Simons, M, Maier, EM

J Exp Med 2017
23401004 Rag GTPases mediate amino acid-dependent recruitment of TFEB and MITF to lysosomes

Puertollano, R, Martina, JA

J Cell Biol 2013
31123060 MITF-the first 25 years

Arnheiter, H, Goding, CR

Genes Dev 2019
21317285 WIPI1 coordinates melanogenic gene transcription and melanosome formation via TORC1 inhibition

Ganesan, AK, Ho, H, Al-Tahan, S, Ahmad, S, Kapadia, R

J Biol Chem 2011
24477476 Novel roles for the MiTF/TFE family of transcription factors in organelle biogenesis, nutrient sensing, and energy homeostasis

Puertollano, R, Martina, JA, Li, H, Diab, HI

Cell Mol Life Sci 2014
26761346 Drosophila Mitf regulates the V-ATPase and the lysosomal-autophagic pathway

Botas, J, Ballabio, A, Bouché, V, Sardiello, M, Espinosa, AP, Leone, L

Autophagy 2016
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Authored
Rothfels, K  (2023-12-21)
Reviewed
de la Serna, IL  (2024-05-21)
Arnheiter, H  (2024-02-26)
Steingrímsson, E  (2024-11-05)
Vu, HN  (2024-11-05)
Created
Rothfels, K  (2024-01-14)
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