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. 2025 Dec 6.
doi: 10.1038/s41598-025-31265-x. Online ahead of print.

TRIP13 alters mitochondrial function and promotes bortezomib resistance in multiple myeloma

Yang Chen #  1 , Yule Liu #  2 , Yuan Wang  3 , Daoda Qi  1 , Chengyi Peng  1 , Shulun Huang  1 , Jingjing Guo  1 , Zidu Xu  4 , Yan Gu  5
Affiliations
Free article

TRIP13 alters mitochondrial function and promotes bortezomib resistance in multiple myeloma

Yang Chen et al. Sci Rep. .
Free article

Abstract

Bortezomib (BTZ) resistance remains a major therapeutic challenge in multiple myeloma (MM). This study investigates the role of thyroid hormone receptor interactor 13 (TRIP13) in MM progression and BTZ resistance. Analysis of public datasets and clinical bone marrow samples revealed that TRIP13 is significantly upregulated in MM and that its expression correlates with advanced disease stage and poor overall survival. In vitro, TRIP13 overexpression (TRIP13-OE) in MM cell lines significantly enhanced cell proliferation, reduced BTZ-induced apoptosis, and alleviated G2/M cell cycle arrest. Functional assays further showed that TRIP13-OE cells preserved mitochondrial membrane potential, reduced mitochondrial calcium overload, and maintained ATP production following BTZ exposure. Quantitative polymerase chain reaction (qPCR) analysis demonstrated that mitochondrial regulatory genes were upregulated in TRIP13-OE cells, particularly mitochondrial calcium uniporter (MCU). Co-immunoprecipitation following BTZ treatment confirmed a specific interaction between TRIP13 and MCU, while immunofluorescence labeling showed their cytoplasmic co-localization. These findings uncover a previously unrecognized role of TRIP13 in regulating mitochondrial integrity under proteotoxic stress, thereby contributing to BTZ resistance. Targeting TRIP13 may represent a novel therapeutic approach to improve outcomes in MM patients.

Keywords: Bortezomib resistance; MCU; Mitochondrial function; Multiple myeloma; TRIP13.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: This study was approved by the Medical Ethics Committee of Nanjing Second Hospital (No. 2023-LY-ky-052).

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