Although mitochondria have long been considered the powerhouse of the living cell, it is only recently that we have been able to employ these organelles for electrocatalysis in electrochemical energy conversion devices. The concept of using biological entities for energy conversion, commonly referred to as a biofuel cell, has been researched for nearly a century, but until recently the biological entities were limited to microbes or isolated enzymes. However, from the perspectives of efficient energy conversion and high volumetric catalytic activity, mitochondria may be a possible compromise between the efficiency of microbial biofuel cells and the high volumetric catalytic activity of enzymatic biofuel cells. This perspective focuses on comparing mitochondrial biofuel cells to other types of biofuel cells, as well as studying the fuel diversity that can be employed with mitochondrial biofuel cells. Pyruvate and fatty acids have previously been studied as fuels, but this perspective shows evidence that amino acids can be employed as fuels as well.