Skip to main content
. Author manuscript; available in PMC: 2023 Nov 24.
Published in final edited form as: Cell Rep. 2023 Oct 17;42(10):113260. doi: 10.1016/j.celrep.2023.113260

Figure 4. Circuit threshold and delay behaviors are differentially affected by mutations affecting Parkin activation dynamics.

Figure 4.

(A) Parkin domain map with location of mutations. UBL: ubiquitin-like. ACT: activating. REP: repressive. Four RING-like domains: RING0, RING1, IBR (in between RING), and RING2.

(B) Effect of selected Parkin mutations on the competition-driven domain rearrangements during parkin activation. UBCH7: an E2 Ub ligase responsible for charging Parkin.23 Inset: unphosphorylated W403A Parkin is partially active. T-bars: repression. For effects in context of full circuit, see Figure S4A.

(C) Effect of Parkin mutations on PINK1 input threshold and reciprocal activation delay. n.d.: not determined due to lack of Parkinmito recruitment. Means, 95% confidence intervals, and statistical significance calculated by bootstrap analysis (B = 10,000; STAR Methods) of fixed cell populations in Figure S4C. Bonferroni multiple comparison adjustment. ***p < 0.001; n.s.: not significant.

(D) S228D PINK1 rescue of R104A Parkin. Representation and analysis as in (C). Single-cell data is shown in Figure S4E. See also Figure S4.