Research Paper Advance Articles
Cisd1 synergizes with Cisd2 to modulate protein processing by maintaining mitochondrial and ER homeostasis
- 1 International Master Program for Translation Science, College of Medical Science and Technology, Taipei Medical University, New Taipei City 23564, Taiwan
- 2 The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 11529, Taiwan
- 3 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei 11031, Taiwan
- 4 International Ph.D. Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan
- 5 Master Program in Clinical Genomics and Proteomics, School of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
- 6 Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- 7 Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan
- 8 Center of General Education, Chang Gung University, Taoyuan 333, Taiwan
- 9 Center for Healthy Longevity and Aging Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
- 10 Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan 350, Taiwan
Received: May 22, 2024 Accepted: March 24, 2025 Published: May 8, 2025
https://doi.org/10.18632/aging.206249How to Cite
Copyright: © 2025 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Connection and crosstalk among the organelles critically contribute to cellular functions. Destruction of any kind of organelle is likely to induce a series of intracellular disorders and finally lead to cell death. Because of its subcellular locations, CDGSH iron-sulfur domain-containing protein 1 (Cisd1) and Cisd2 have functions that are related to maintaining mitochondria and ER homeostasis. As previous reports have shown, Cisd2 knockout mice have a decreased body weight and poor survival rate, and the primary defects were conducted in skeletal muscle. Our previous findings indicated that Cisd1 deletion causes a range of skeletal muscle defects in mice with Cisd2 deficiency, including mitochondrial degeneration, endoplasmic reticulum (ER) stress, and alteration of protein process, as well as programmed cell death. In Cisd1 and Cisd2 deficient condition, the whole of the protein biosynthesis was damaged, including translation, modification, transport, and degradation. Changes in the immune response, redox regulation, and metabolism were also present in Cisd1 and Cisd2 double knockout mice. Overall, we have demonstrated that Cisd1 and Cisd2 knockout have a synergistic effect on skeletal muscles, and that Cisd2 plays a more critical role than Cisd1. These synergistic effects impact signaling regulation and interrupt the crosstalk and homeostasis of organelles. This creates severe disorders in various tissues and organs.