An intrinsically disordered domain has a dual function coupled to compartment-dependent redox control

Area of Science:

• Cell Biology
• Protein Science
• Mitochondrial Biology

Background:

• Intrinsically disordered proteins (IDPs) are crucial in cellular processes.
• The role of intrinsically disordered domains (IDDs) in mitochondrial targeting and biogenesis remains largely unknown.
• Sulfhydryl oxidase ALR (augmenter of liver regeneration) is located in the mitochondrial intermembrane space.

Purpose of the Study:

• To characterize the structural, dynamic, and functional properties of an IDD in the mitochondrial sulfhydryl oxidase ALR.
• To investigate the involvement of IDDs in mitochondrial targeting and function.
• To explore the potential dual roles of IDDs in different cellular compartments.

Main Methods:

• Structural and dynamic characterization of the ALR IDD.
• Functional assays to assess mitochondrial targeting.
• Analysis of the role in the disulfide relay system within the intermembrane space.

Main Results:

• The ALR IDD does not undergo significant structural changes upon substrate recognition or redox switching.
• The IDD functions as a mitochondrial targeting signal in the cytosol.
• The IDD serves as a critical recognition site in the mitochondrial intermembrane space's disulfide relay system.

Conclusions:

• The characterized IDD of ALR exhibits a dual function, acting in distinct cellular compartments.
• This finding presents a novel paradigm for intrinsically disordered domains, linking them to intracellular organelle targeting.
• IDDs can mediate distinct functions essential for mitochondrial biogenesis and function.