In cells, there are many kinds of functional "micro-organs" called organelles. Mitochondria are the energy-producing organelles in the cell and are known as the "power plant" of the cell.
Mitochondria have a complex structure that is divided into four regions from the inside out, the outer (OM) and inner membrane (IM) and the two soluble compartments intermembrane space (IMS) and matrix. Mitochondria are highly dynamic, fusing and dividing with each other constantly. Among the known regulatory proteins of mitochondrial dynamics, OPA1 is a key regulator participating in mitochondrial inner membrane fusion.
OPA1 protein has two different forms, a long chain form anchored to the inner membrane and a short chain form free in the IMS. Recent studies have revealed that OPA1 has well-established roles in multiple physiological processes such as mitochondrial dynamics, energetics, mtDNA maintenance, apoptotic cristae remodeling, apoptosis, cellular redox homeostasis, and aging.
Molecular chaperones are a class of proteins that assist in the assembly of intracellular molecules and assist in the folding of proteins. Although the three-dimensional structure of a protein is determined by its own amino acid sequence, not all proteins fold naturally to their native state, i.e., the final state in which the protein can perform its function, and many proteins often require the assistance of molecular chaperones to reach or return to their natural state after folding or inactivation at high temperatures.
Most mitochondrial proteins are synthesized on cytosolic ribosomes, and then imported, across IMS, into mitochondria. As mitochondrial IMS is an oxidative environment, proteins therein are likely to confront with adverse conditions emanating from the respiratory chain. These proteins could play a wide range of and critical functions. Therefore, protection of these IMS proteins should be essential for maintaining an optimal function of mitochondria. However, few protective molecular chaperones were found in the mitochondrial IMS.
In an article published by Dr. Liu Xingguo and his partners at Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, these researchers stated: “Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space.”
The researchers revealed in the study, which was published in the Science China life sciences, that the soluble short-chain protein (S-OPA1) sheared at the IMS under stress conditions, serves as a molecular chaperone and is used to maintain the proteostasis of the IMS. The S-OPA1 protein was first purified in vitro, showing that it protected substrate proteins from thermal and chemically induced aggregation and improved bacterial resistance to thermal stimulation.
The researchers further determined that S-OPA1 protects mitochondrial IMS proteins under heat shock by using OPA1 knockout cells and S-OPA1overexpressed cells and combined with mass spectrometry and immunoprecipitation techniques identified neurolysin as one of its protective proteins. This new function of S-OPA1 may contribute to sustain mitochondrial homeostasis.
This research was funded by the National Key Research and Development Program of China (2017YFA0106300), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030505).
See the article:
Yao, D., Y. Li, S. Zeng, Z. Li, Z. Shah, B. Song, J. Liu, Y. Wu, L. Yang, Q. Long, W. Wang, Z. Hu, H. Tang, & X. Liu * (2021) Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space. SCIENCE CHINA Life Sciences. https://doi.org/10.1007/s11427-021-1962-0
Science China Life Sciences