TableS1

Functionally relevant mutation sites in the human mitochondrial respiratory complex 1 (MT-C1)

Supplement to "OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and a prognostic gene expression signature" by B.Schöpf, H.Weissensteiner, G.Schäfer, F.Fazzini, P.Charoentong, A.Naschberger, B.Rupp, L.Fendt, V.Bukur, I.Eichelbrönner, P.Sorn, U.Sahin, F.Kronenberg, E.Gnaiger, H.Klocker.

Overview of the MT-C1:

The transmenbrane region harboring the ND domains is shown as a yellow macrosphere. The

ribbon diagram shows the individual peptide chains of the complex in different colors, highlighting the

ND-domain core (colored as in Figure 4G), in which mutations associated with a high prostate cancer malignancy score (GLSN) are located.

Click on any native residue and then on the mutation to zoom in on the detail. Return to the ND-domain core overview between detail views for orientation.

Functionally relevant mutations
ID	GLSN	L %	Gene	Locus	Mutation	Possible explanation based on human mitochondrial respiratory complex structure
PK_30	10	23	MT-ND1	G3907A	A 201 T	Change from small hydrophobic to polar residue in hydrophobic environment. Likely destabilizes the structure due to incompatible larger polar residue.
PK_44	9	30	MT-ND2	T5359C	I 297 T	Change from hydrophobic to polar residue in hydrophobic environment. Likely destabilizes the structure due to incompatible polar residue.
PK_34	7	38	MT-ND3	T10326C	S 90 P	Substitution of polar H-bonded serine residue in an α-helix with the helix-breaking proline likely destabilizes the secondary/tertiary structure.
PK_81	9	60	MT-ND3	G10353A	A 99 T	Change from hydrophobic to polar residue located on the surface of a trans-membrane helix pointing towards the membrane site. Helix may lose hydrophobic interaction needed for proper membrane insertion.
PK_32	7	85	MT-ND4	T12131C	S 458 P	Located at the C-terminus of ND-4. Loss of polar interaction and reduced conformational freedom of proline could destabilize structure.
PK_96	10	82	MT-ND4	T11991C	F 411 S	Change from large hydrophobic to small polar residue within a hydrophobic interaction network can significantly destabilize the structure.
PK_97	8	59	MT-ND4L	T10551C	S 28 P	Substitution of polar H-bonded serine residue in an α-helix with the helix-breaking proline eliminates 2 hydrogen bonds and destabilizes the structure.
PK_63	7	81	MT-ND5	A13495G	T 387 A	Located in loop of a discontinuous helix in the central axis of the CI membrane domain believed to be important for proton pumping. Loss of H-bond may trigger conformational change.
PK_95	7	55	MT-ND5	T12805C	W 157 R	Change from large hydrophobic to charged residue within large entropic freedom. Destabilizing disturbance of hydrophobic interaction network.
PK_66	7	39	MT-ND6	G14663A	A 4 V	Conserved substitution (small hydrophobic to larger hydrophobic). No obvious explanation from structural point of view.