Coordinated membrane remodeling and fission-fusion drive mitochondrial patterning during development

Abstract

How complex organelles remodel their architecture during development remains a fundamental question in cell biology. Using the Drosophila nebenkern, a giant multilamellar mitochondrion that transforms into two elongated mitochondrial derivatives during spermiogenesis, we dissect the challenges underlying large organelle morphogenesis. We show that this transformation is achieved through coordinated control of fusogenicity, membrane geometry, and membrane redistribution. PINK1/Parkin-dependent downregulation of the mitofusin Marf reduces mitochondrial fusogenicity and stabilizes organelle separation following division. Concurrently, membrane tubulation establishes a geometric template for DRP1 recruitment, specifying a deterministic fission plane within a large mitochondrial sheet structure. Mitochondrial elongation is accompanied by the formation of mitochondria-derived inverted vesicles (MDiVs), previously undescribed double-membraned structures that may redistribute membrane through inward budding independently of canonical fission and fusion. More broadly, our work establishes a framework for understanding how membrane geometry, regulated fusogenicity, and vesicle-mediated remodeling cooperate to generate complex organelle architectures during development. Significance statementLarge organelles pose unique challenges for scaling and division because canonical membrane dynamics must be coordinated across extensive membrane architectures. Using a giant multilamellar mitochondrial structure as a model, we show that organelle morphogenesis is achieved through independent yet coordinately regulated mechanisms that spatially pattern division, stabilize partitioning, and redistribute membranes through intraorganellar vesicles with an inverted topology. These findings reveal principles of organelle morphogenesis that extend beyond conventional fission-fusion models.