TMEM135

Last update 08 May 2025

Basic Info

Synonyms

FLJ22104, Peroxisomal membrane protein 52, PMP52

+ [2]

Introduction

Involved in mitochondrial metabolism by regulating the balance between mitochondrial fusion and fission. May act as a regulator of mitochondrial fission that promotes DNM1L-dependent fission through activation of DNM1L. May be involved in peroxisome organization.

100 Clinical Results associated with TMEM135

100 Translational Medicine associated with TMEM135

0 Patents (Medical) associated with TMEM135

Literatures (Medical) associated with TMEM135

01 Apr 2025·Hearing Research

A mutation in Tmem135 causes progressive sensorineural hearing loss

Article

Author: Park, Hyo-Jin ; Ikeda, Akihiro ; Simms, Shion ; Milani, Marcus ; Suzuki, Jun ; Behnammanesh, Ghazaleh ; Someya, Shinichi ; Chen, Wei-Wen ; Kim, Mi-Jung ; Katori, Yukio ; Honkura, Yohei ; Bird, Jonathan E

Transmembrane protein 135 (TMEM135) is a highly conserved 52 kDa protein with five predicted transmembrane domains that colocalizes with mitochondria and peroxisomes. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism across multiple tissues and species; however, its role in the inner ear and auditory system remains unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135^{FUN025/FUN025} (FUN025) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) thresholds at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing results, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and more modest changes in inner hair cell survival, spiral ganglion neuron density, and stria vascularis integrity in the cochlea. Our results using BaseScope RNA in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, supporting cells, and stria vascularis. Using Volocity software and Costes colocalization analysis, we found that TMEM135 closely colocalizes with mitochondria in hair cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

01 Feb 2025·Molecular Metabolism

TMEM135 deficiency improves hepatic steatosis by suppressing CD36 in a SIRT1-dependent manner

Article

Author: Park, Channy ; Wei, Xiaofan ; Kwon, Hyug Moo ; Lee, Sang-Wook ; Manandhar, Laxman ; Park, Raekil ; Hwang, Jaetaek ; Kim, Hyunsoo ; Chinbold, Batching ; Chuluunbaatar, Chagtsalmaa ; Chhetri, Arun ; Jang, Gyuho

OBJECTIVESDysregulation of lipid homeostasis pathway causes many liver diseases, including hepatic steatosis. One of the primary factors contributing to lipid accumulation is fatty acid uptake by the liver. Transmembrane protein 135 (TMEM135), which exists in mitochondria and peroxisomes, participates in intracellular lipid metabolism. This study aims to investigate the role of TMEM135 on regulating cellular lipid import in the liver.METHODSWe used in vivo, ex vivo, and in vitro models of steatosis. TMEM135 knockout (TMEM135KO) and wild type (WT) mice were fed a high-fat diet (HFD) to induce hepatic steatosis. Primary mouse hepatocytes and AML12 cells were treated with free fatty acid (FFA). Additionally, TMEM135-deficient stable cells and overexpressed cells were established using AML12 cells.RESULTSTMEM135 deficiency mitigated lipid accumulation in the liver of HFD-fed TMEM135KO mice. TMEM135-depleted primary hepatocytes and AML12 cells exhibited less lipid accumulation when treated with FFA compared to control cells, as shown as lipid droplets. Consistently, the effect of TMEM135 depletion on lipid accumulation was completely reversed under TMEM135 overexpression conditions. CD36 expression was markedly induced by HFD or FFA, which was reduced by TMEM135 depletion. Among the SIRT family proteins, only SIRT1 expression definitely increased in the liver of HFD-fed TMEM135KO mice along with a significant increase in NAD⁺/NADH ratio. However, inhibition of SIRT1 in TMEM135-depleted cells using siSIRT1 or the SIRT1 inhibitor EX-527 resulted in an increase of CD36 expression and consequent TG levels.CONCLUSIONSTMEM135 depletion attenuates CD36 expression in a SIRT1-dependent manner, thereby reducing cellular lipid uptake and hepatic steatosis.

01 Jan 2025·Advances in Experimental Medicine and Biology

Association Between C22:5-Containing Lipids and RPE Pathologies in Mice with Tmem135 Overexpression

Article

Author: Landowski, Michael ; Ikeda, Sakae ; Ikeda, Akihiro

Dysregulation of lipid metabolism has been linked with risk for age-related retinal diseases including age-related macular degeneration (AMD). However, how dysregulated lipid metabolism contributes to AMD development is unknown. In this study, we evaluated the retinal and plasma lipidomes of a mouse model displaying retinal pigmented epithelium (RPE) pathologies that are observed in AMD including RPE dysmorphia and degeneration. We found that the RPE phenotypes in mice overexpressing transmembrane protein 135 (Tmem135 TG) are correlated with retinal and plasma lipidome changes. While distinct lipid profiles were observed in the retina and plasma of Tmem135 TG mice, a common finding in both retinal and plasma lipidomes was an increase of lipids containing C22:5. This data suggests that accumulation of C22:5-containing lipids may contribute to the development of the RPE pathologies in Tmem135 TG mice.

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TMEM135

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