Reply to Bailey et al.: New perspectives on the novel role of the Poldip2/ACSM1 axis in a functional mammalian lipoylation salvage pathway

We appreciate Bailey et al.’s (1) interest in our publication (2), in which we define a role for polymerase-δ interacting protein 2 (Poldip2) in controlling a salvage pathway of lipoylation. Our study builds on a substantial body of evidence, indicating that the mammalian mitochondrial lipoyltransferase LIPT1 lipoylates using lipoyl-AMP. While sharing sequence homology with the bacterial lipoate-protein ligase A (lplA), LIPT1 is distinct in that it catalyzes only the last of the two-step reaction that involves activation of lipoate (yielding lipoyl-AMP as an intermediate), followed by transfer to the apoenzyme (3). Thus, in contrast to lplA, LIPT1-dependent protein lipoylation occurs only when provided with lipoyl-AMP, indicating that it uses activated … [↵][1]1To whom correspondence should be addressed. Email: asanmartin{at}emory.edu. [1]: #xref-corresp-1-1