Abnormal mitochondrial aggregations in TDP-43
mice. COX-IV immunoreactivity illustrates densely stained aggregates in a spinal motor neuron of (A) TDP-43M337V mice, but not in (B) NT mice. (C) Electron micrograph of a spinal motor neuron from a TDP-43M337V mouse shows a cluster of mitochondria surrounding a filamentous core (boxed area). (D) Enlargement of the filamentous core showing 20 nm filaments and various vesicles. Small dense granules are stain precipitates. (E) Electron micrograph of a mitochondrial aggregate in another spinal motor neuron of the TDP-43M337V mouse. Note the close proximity of mitochondria with varying degrees of degenerating inner cristae (arrowheads), compared to normal mitochondria in motor neurons of (F) NT mice. (E) The degenerating mitochondria of TDP-43M337V mice also appear smaller in size compared with those of (F) NT mice. Asterisk in (E) indicates a vacuolated mitochondrion. (F) In NT mice, mitochondria (arrows) were usually separated by other cytoplasmic organelles, e.g. rough endoplasmic reticulum (arrowheads) and ribosomes. Scale bars: 50 μM in A and B.