TP-2846 binds to the mitochondrial ribosome
, inhibiting protein translation and inducing apoptosis.
Analysis of white blood cells from patients with early AD shows that the expression of mitochondrial respiratory complex I-V genes and subunits of the core mitochondrial ribosome
complex are decreased compared to controls .
(29) Based on the first theory, mRNA translation may be utilized by extra mitochondrial ribosomes
and the second theory states that mRNA translation may be performed by intra mitochondrial ribosomes
Additionally, Schimmer believes it's possible that chemists could design tigecycline analogues that would be more potent or more selective of mitochondrial ribosomes
over bacterial ones.
(2) Here they undergo retrograde transport through the endoplasmic reticulum, where they can interfere with protein sorting and synthesis, (3) and are then transported into the nucleus and mitochondria where they can inhibit mitochondrial ribosomes
(4) (in a way that is analogous to their bactericidal effect on the small ribosomal unit of bacteria).
Although all of the synthesized plastid proteins identified to date are plastid encoded (Mujer et at., 1996; Pierce et at., 1996; Green et at., 2000), two groups of synthesized plastid proteins can be distinguished pharmacologically: those inhibited by cycloheximide (CHX), an 80S cytosolic ribosome inhibitor (Obrig et at., 1971), and those inhibited by chloramphenicol (CAP), which inhibits protein synthesis on 70S plastid and mitochondrial ribosomes (Lamb et at., 1968; Stone and Wilke, 1975).
CHX (2 mg [ml.sup.-1] was used to inhibit protein synthesis on 80S cytosolic ribosomes; CAP (160 [micro]g [ml.sup.-1]; stock concentration 50 mg [ml.sup.-1] in absolute ethanol) was used to inhibit translation on 70S plastid and mitochondrial ribosomes. Two to four slugs, total wet weight about 1.25 g, were placed into glass scintillation vials containing ASW (1000 mosm) and the appropriate inhibitor, and incubated under intense light (150 W, GE Cool Beam incandescent indoor flood lamp) at 20 [degrees]C in a gently agitating water bath.
Although ATAD3 appeared to be bound to the D-loop of mtDNA in nucleoid , subsequent experiments indicated that ATAD3 made direct contact with mtDNA but is among the nucleoid-associated proteins involved in connections between mitochondrial nucleoids and mitochondrial ribosomes