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Why does most mitochondrial protein information come from DNA in the cell nucleus?

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Fluorescent confocal image of HeLa cells with green microtubules outlining cell shapes, red mitochondria, and blue nuclei. — mitochondrion Mitochondria (red) are found throughout the cytoplasm of almost all eukaryotic cells (cell nucleus is shown in blue; cytoskeleton is shown in yellow).

Most mitochondrial proteins originate from the cell nucleus because, over evolutionary time, the ancestral prokaryotic endosymbiont that became the mitochondrion underwent significant genome reduction.12

While mitochondria retain a small, unique genome—containing 37 genes in humans—this is insufficient to encode the vast array of proteins required for the organelle's complex functions. Consequently, the majority of the genetic instructions for mitochondrial proteins are housed within the nuclear genome. These proteins are synthesized on ribosomes in the cytosol and are subsequently transported into the mitochondria, guided by specific signal sequences that ensure they reach their correct destination within the organelle.13