Figure 6.

Developmentally orchestrated mitochondrial processes in Dm germarium prime selective inheritance, limiting the transmission of deleterious mtDNA mutations. Mitochondria are mostly interconnected in the anterior part of the germarium. Mitochondrial fragmentation in dividing cysts, together with the lack of mtDNA replication, promotes mtDNA segregation in dividing cysts and region 2A. The effective mtDNA segregation minimizes the potential complementation among different mitochondrial genotypes. After mtDNA segregation, mtDNA transcription begins, which supports ETC biogenesis and activates mitochondrial respiration in 16-cell cysts at region 2B. The expression of mtDNA hence acts as a stress test for its integrity: mitochondria containing wild-type genome will be active, whereas mitochondria afflicted by deleterious mutations will be depolarized. mtDNA replication begins at region 2B and depends on mitochondrial activity. Healthy mitochondria containing wild-type mtDNA propagate much more vigorously than organelles containing deleterious mutations. These coordinated events act synergistically to restrict the transmission of detrimental mtDNA mutations in the female germline. The Balbiani body (BB) in the oocyte also contributes to selective inheritance by furnishing healthy mitochondria to the germ plasm.

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