Practice question

Cytosolic steps preceding mitochondrial import require chaperoning maintain precursors loosely folded translocation competent capable threading narrow TOM 20 angstrom channel. Nascent chains emerging ribosome contain hydrophobic segments aggregation-prone aqueous cytosol. Cytosolic Hsp70 family mainly Ssa1-4 yeast and HSPA1A HSPA8 mammals with co-chaperones Ydj1 Sis1 J-domain stimulating ATPase nucleotide exchange Sse1 Bag family bind exposed hydrophobic patches substrate binding domain ATP-dependent holdase preventing misfolding self-association aggregation delivering precursors Tom70 receptor tetratricopeptide clamp binding Hsp70 EEVD motif. Cycling ATP-bound low affinity ADP-bound high affinity regulated ATP hydrolysis tightens grip NEF-triggered ADP release loosens. Within IMS matrix distinct Hsp70 paralogs Tim14-16 mtHsp70 provide directional pulling motor. Hsp70 does not directly degrade misfolded precursors though may recruit CHIP E3 triaging aggregates proteasome does not block TOM channel opening does not generate vesicles mitochondrial transport occurs soluble chaperoned diffusion. Depletion cytosolic Hsp70 cytosolic precursor foci aggregates reduced import illustrating protective role essential mitochondrial biogenesis preventing proteotoxic stress and maintaining proteostasis cellular health and viability.