Related Experiment Video
Updated: Jun 24, 2025
08:33
Author Spotlight: An Optimized Automated Method for Investigating Retinoic Acid Receptors in Neuronal Mitochondria
Published on: July 28, 2023
607
TRABD modulates mitochondrial homeostasis and tissue integrity
Caixia Zhou1, Zhirong Li1, Yawen Li1
1MOE Key Laboratory for Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Gastroenterology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Cell Reports
|June 6, 2024
Summary
Translocase of inner mitochondrial membrane domain-containing protein B (TRABD) is a mitochondrial protein linked to Alzheimer's disease. Its dysfunction contributes to age-related neurodegeneration by affecting mitochondrial structure and function.
Area of Science:
- Mitochondrial biology
- Neuroscience
- Cellular aging
Background:
- High TRABD expression correlates with tau pathology in Alzheimer's disease patients.
- The precise function of TRABD in cellular processes and disease remains largely unknown.
Purpose of the Study:
- To elucidate the function of TRABD in mitochondrial dynamics and its role in neurodegeneration.
- To investigate the impact of TRABD on mitochondrial morphology, fusion, and age-related pathologies.
Main Methods:
- Investigated human TRABD's localization and function in mitochondrial outer membrane.
- Utilized Drosophila melanogaster (fruit fly) models to study dTRABD's role in aging and neurodegeneration.
- Analyzed mitochondrial morphology, fusion, reactive oxygen species (ROS), and ATP production.
Main Results:
- TRABD loss causes mitochondrial fragmentation; overexpression induces clustering and fusion.
- TRABD interacts with MFN2, MIGA2, and PLD6 to mediate mitochondrial fusion.
- Aging flies show reduced dTRABD expression, while overexpression exacerbates neurodegeneration and tau toxicity, increasing ROS and ATP production.
Conclusions:
- TRABD is a key regulator of mitochondrial fusion and dynamics.
- TRABD-induced mitochondrial dysfunction is implicated in age-related neurodegeneration and tau pathology.
More Related Videos
Related Concept Videos
01:45Mitochondrial Membranes
10.0K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
10.0K
01:46Electron Transport Chain: Complex I and II
13.0K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
13.0K
01:19Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
01:28The Inner Mitochondrial Membrane
3.3K
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
3.3K
01:37Mitochondria
12.2K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
12.2K
01:39Mitochondrial Protein Sorting
4.3K
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.3K