The biogenesis of mitochondria depends on sophisticated import machineries to correctlytarget and fold cytosolically synthesized mitochondrial proteins. The mitochondrial import and
assembly (MIA) pathway is a redox relay system that is essential for protein import into the
intermembrane space (IMS) of mitochondria. It is unique that protein oxidation is tightly coupled
to protein translocation. Given that the intermembrane space is highly relevant to a broad
spectrum of diseases including apoptosis and neurodegeneration, additional research is needed to
understand the underlying mechanism and new roles of regulation by the redox relay system.
We have identified a novel protein, Aim32 that is dually localized in matrix and IMS.
Aim32 is a thioredoxin-like [2Fe-2S] ferredoxin protein and binds with Erv1. Deletion of Aim32
or mutation of conserved cysteine residues resulted in an increased accumulation of proteins with
aberrant disulfide linkages. In addition, the steady-state level of assembled mitochondrial protein
import complexes was decreased, and a subset of the complexes showed disassembly. Aim32
also bound to several mitochondrial proteins through disulfide linkages, suggesting a function in
maintaining the redox status of proteins by potentially targeting cysteine residues. These studies
suggest that Aim32 may be poised as a sensor or regulator in quality control in a broad range of
mitochondrial proteins.
In addition to the function of ALR/Erv1 in protein translocation, it plays critical roles in
various cellular pathways. We found ALR/Erv1 has an unexpected pro-survival role in hPSCs. A
small molecule inhibitor that is specific for ALR/Erv1 was applied to investigate the hPSCs
apoptosis and differentiation, which has the potential in hPSCs therapeutics
