A fascinating story is unfolding at the interface between mitochondria and the ER. Two new papers, one in this issue of The EMBO Journal (Wu et al, 2016) and one in the journal Autophagy (Chen et al, 2016), further clarify the role of mitochondrial outer membrane protein FUNDC1 in autophagy and connect it to mitochondrial fission occurring at the interface between mitochondria and the ER.
See also: W Wu et al
Several years ago, the laboratory of Quan Chen discovered a new mitochondrial outer membrane protein required for mitophagy when it is induced by hypoxia (Liu et al, 2012). This protein, called FUNDC1 (Fun14 domain containing protein 1), is anchored in the mitochondrial outer membrane by three predicted transmembrane segments. The cytosolic N‐terminal domain of FUNDC1 has a LIR (an LC3 interacting region) that helps recruit autophagic isolation membrane to mitochondria under hypoxic conditions. Whether and how FUNDC1 would be concomitantly linked to mitochondrial dynamics such as fission and fusion remained unclear. New work now shows that FUNDC1 exerts its function at the interface between mitochondria and the ER and thereby controls mitochondrial dynamics and mitophagy.
The interface between mitochondria and the ER, which is commonly referred to as the MAM (mitochondrion associated membrane), performs a plethora of functions (Phillips & Voeltz, 2016). The MAM brings together key signaling pathways that help decide between apoptosis and autophagy in response to cellular stress. It is furthermore involved in calcium transfer between the organelles through close coupling of uptake and release channels. The MAM also facilitates the transfer of lipids between the organelles …