Abstract
Tom70 is a versatile adaptor protein of 70 kDa anchored in the outer membrane of mitochondria in metazoa, fungi and amoeba. The tertiary structure was resolved for the Tom70 of yeast, showing 26 α-helices, most of them participating in the formation of 11 tetratricopeptide repeat (TPR) motifs. Tom70 serves as a docking site for cytosolic chaperone proteins and co-chaperones and is thereby involved in the uptake of newly synthesized chaperone-bound proteins in mitochondrial biogenesis. In yeast, Tom70 additionally mediates ER-mitochondria contacts via binding to sterol transporter Lam6/Ltc1. In mammalian cells, TOM70 promotes endoplasmic reticulum (ER) to mitochondria Ca2+ transfer by association with the inositol-1,4,5-triphosphate receptor type 3 (IP3R3). TOM70 is specifically targeted by the Bcl-2-related protein MCL-1 that acts as an anti-apoptotic protein in macrophages infected by intracellular pathogens, but also in many cancer cells. By participating in the recruitment of PINK1 and the E3 ubiquitin ligase Parkin, TOM70 can be implicated in the development of Parkinson’s disease. TOM70 acts as receptor of the mitochondrial antiviral-signaling protein (MAVS) and thereby participates in the corresponding system of innate immunity against viral infections. The protein encoded by Orf9b in the genome of SARS-CoV-2 binds to TOM70, probably compromising the synthesis of type I interferons.
Highlights
Mitochondria have fascinated researchers across all disciplines of life science for over a century [1]
It was concluded that Tom70 is a protein with the specific function to direct the members of a limited class of newly synthesized preproteins to the general import pore of the mitochondria, thereby serving a limited but well defined and specific purpose in the cell
Tom70 was known as a protein in two different fungi, yeast and Neurospora crassa, and it was unknown if human cells may have a similar protein, or possibly a completely different system of mitochondrial protein import
Summary
Mitochondria have fascinated researchers across all disciplines of life science for over a century [1]. Subsequent studies showed that the TOM complex contains several additional components and cooperates with independent complexes of other outer membrane proteins, but they essentially confirmed the basic scheme of distinct receptor proteins, one of them being Tom, cooperating with a general import pore [3,4] (see below, Figure 5). Tom is an outer membrane protein that associates with Tom only partially and in a reversible manner Why is it useful to review the current state of research on a protein that was characterized 30 years ago, if the basic scheme of its function seems to be retained? FFiigguurree 1.1.CeClluelllaurlfaurncftuionncstioofntsheomf ittohcehonmdirtoiaclhoountderrimalemoburtaenre pmreomtebinraTnoem7p0r.oItMeiSn, inTtoermm7e0m. bIrManSe, sinptaecrem; MemObMra,nmeistopcahcoe;nMdrOiaMl o,umteitromcheomnbdrrainale;oTuOteMr m, termanbsrloacnaes;eToOfMth,etrmanitsolcohcoansedroifatlhoeumteritomcehmonbdrarniael, coountetarimnienmg bthraenceh,acnonnetla-ifnoirnmginthgepcrhoatneinneTl-ofomrm40inagndprthoteeiimn pToormt 4re0caenpdtotrhTeoimm2p0o.rt receptor Tom
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