Mitochondrial inner membrane fusion protein acts as a molecular chaperone

Cells contain numerous functional “micro-organs” known as organelles. Mitochondria, the “power plant” of the cell, are the energy-producing organelles.

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Mitochondria comprise a complex structure that is divided into four regions from the inside out—the outer membrane (OM), inner membrane (IM), and the two soluble compartments intermembrane space (IMS) and matrix. Mitochondria are increasingly dynamic, fusing, and dividing with each other continually.

Amidst the known regulatory proteins of mitochondrial dynamics, OPA1 is a major regulator taking part in mitochondrial inner membrane fusion.

There are two different forms in OPA1 protein, a short-chain form free in the IMS and a long chain form fastened to the inner membrane. Current research works show that OPA1 has significant roles in various physiological mechanisms like mitochondrial energetics, dynamics, mtDNA maintenance, apoptosis, apoptotic cristae remodeling, cellular redox homeostasis, and aging.

Molecular chaperones, a class of proteins, help in the assembly of intracellular molecules and assist in the folding of proteins. Even though the 3D structure of a protein depends on its amino acid sequence, not all proteins fold naturally to their native state, i.e., the final state in which the protein can carry out its function.

The majority of the proteins often need the assistance of molecular chaperones to reach or return to their natural state after folding or when inactivated at greater temperatures.

The majority of the mitochondrial proteins are produced on cytosolic ribosomes and are later imported, across IMS, into mitochondria. Since mitochondrial IMS is an oxidative environment, proteins therein are likely to tackle detrimental conditions originating from the respiratory chain. The proteins perform a major role in vital functions.

Hence, the protection of these IMS proteins is vital for retaining the optimal function of mitochondria. But a few protective molecular chaperones are seen in the mitochondrial IMS.

In the study published by Dr Liu Xingguo and his associates from the Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, the scientists said, “Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space.”

The scientists demonstrated in the research published in the Science China Life Sciences that the soluble short-chain protein (S-OPA1) sheared at the IMS under stress conditions functions as a molecular chaperone, and is employed to retain the proteostasis of the IMS.

The S-OPA1 protein was initially purified in vitro, displaying that it safeguards substrate proteins from thermal and chemically induced aggregation and enhanced bacterial resistance to thermal stimulation.

The scientists then revealed that S-OPA1 safeguards mitochondrial IMS proteins under heat shock by employing OPA1 knockout cells and S-OPA1 overexpressed cells. They combined immunoprecipitation and mass spectrometry techniques to pinpoint neurolysin as one of its protective proteins. This novel function of S-OPA1 might contribute to maintaining mitochondrial homeostasis.