Reference Report

Reference
Citation	Sugiyama, S., Moritoh, S., Furukawa, Y., Mizuno, T., Lim, Y.M., Tsuda, L., Nishida, Y. (2007). Involvement of the mitochondrial protein translocator component Tim50 in growth, cell proliferation and the modulation of respiration in Drosophila. Genetics 176(2): 927--936. (Export to RIS)
FlyBase ID	FBrf0200675
Publication Type	Research paper
PubMed ID	17435247
PubMed Abstract	Allelic mutants exhibiting growth defects in Drosophila were isolated. Molecular cloning identified the responsible gene as a budding yeast Tim50 ortholog, and thus it was named tiny tim 50 (ttm50). The weak allele (ttm50(Gp99)) produced small flies due to reduced cell size and number, and growth terminated at the larval stage in the strong alleles (ttm50(IE1) and ttm50(IE2)). Twin-spot analysis showed fewer cells in ttm50(Gp99) clones, whereas ttm50(IE1) clones did not proliferate, suggesting that the gene has an essential cellular function. Tim50 is known to maintain mitochondrial membrane potential (MMP) while facilitating inner-membrane protein transport. We found that tagged Ttm50 also localized to mitochondria and that mitochondrial morphology and MMP were affected in mutants, indicating that mitochondrial dysfunction causes the developmental phenotype. Conversely, ttm50 overexpression increased MMP and apoptosis. Co-expression of p35 suppressed this apoptosis, resulting in cell overproliferation. Interestingly, ttm50 transcription was tissue specific, corresponding to elevated MMP in the larval midgut, which was decreased in the mutant. The correlation of ttm50 expression levels with differences in MMP match its proposed role in mitochondrial permeability barrier maintenance. Thus a mitochondrial protein translocase component can play active roles in regulating metabolic levels, possibly for modulation of physiological function or growth in development.
DOI	10.1534/genetics.107.072074
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Secondary IDs
Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Genetics
Title	Genetics
Publication Year	1916-
ISBN/ISSN	0016-6731
Data from Reference
Aberrations (1)
	Df(3L)H99
Alleles (20)
	Avic\GFP^Scer\UAS.cUa BacA\p35^Scer\UAS.cHa CG2712^t3.5 dwg^t3.5 Scer\GAL4^Act5C.PU Scer\GAL4^en-e16E Scer\GAL4^GMR.PF Scer\GAL4^hs.PB Scer\GAL4^ptc-559.1 Scer\GAL4^unspecified th^unspecified ttm50^+t3.5 ttm50^GMR.PS ttm50^Gp99 ttm50^IE1 ttm50^IE2 ttm50^{Scer\UAS.T:Ivir\HA1} w^+mC w^+mW.hs W^unspecified
Constructs (7)
	P{GAL4-Hsp70.PB} P{GAL4-ninaE.GMR} P{GMR-ttm50.S} P{ttm50^+t3.5} P{UAS-GFP.U} P{UAS-p35.H} P{UAS-ttm50.HA}
Genes (12)
	Avic\GFP BacA\p35 CG2712 dwg Scer\GAL4 T:Ivir\HA1 th ttm2 ttm3 ttm50 w W
Insertions (6)
	P{en2.4-GAL4}e16E P{GawB}ptc^559.1 P{UAS-ttm50.HA}2 P{UAS-ttm50.HA}32 P{UAS-ttm50.HA}48 P{unk}ttm50^Gp99
Natural transposons (1)
	P-element