The present disclosure relates to methods and compositions for detecting mitochondrial dysfunction. In particular, the disclosure relates to reporter molecules that are cleavable by the zinc metalloprotease Metalloendopeptidase OMA1 (OMA1). In each embodiment, the reporter molecules of the invention are particularly useful for drug discovery and detection of diseases associated with mitochondrial dysfunction.
1. A reporter molecule comprising:a) a detection domain capable of emitting a signal attached to a linker domain, the linker domain comprising; a Metalloendopeptidase OMA1 cleavage site; b) a repressor domain that represses the signal of said detection domain, wherein the repressor domain is operably linked to the linker domain, and wherein cleavage of said linker domain at said OMA1 cleavage site increases the signal of said detection domain.